Metastatic Breast Cancer News from the 2011 San Antonio Breast Cancer Symposium

Today we'll continue to cover headlines from the 2011 San Antonio Breast Cancer Symposium, with a focus on six studies relevant to women with metastatic breast cancer.

Links may be found on the treatment pages of our LATESTBreastCancer.com website.

Omnitarg for HER2 positive metastatic breast cancer

The phase III Omnitarg (pertuzumab) study, known as CLEOPATRA (CLinical Evaluation Of Pertuzumab and TRAstuzumab), was big news. Reuters, Medical News Today, The New York Times and Los Angeles Times all ran stories. The study was published in the New England Journal of Medicine on December 7. (Link to full text.)

In the study, 808 women with HER2 positive metastatic breast cancer were randomly assigned to receive Herceptin (trastuzumab) and Taxotere (docetaxel) either with or without Omnitarg.

For the Omnitarg group, median progression-free survival, meaning the amount of time the cancer remains stable, was 18.5 months compared to 12.4 months for the Herceptin/Taxotere only group.

Although it's too early to confirm overall survival data, preliminary results show 69 deaths among the 402 women treated with Omnitarg compared to 96 deaths among the 406 women who did not receive Omnitarg.

Genentech and its parent company, Roche, have applied for permission to market Omnitarg in the US and Europe as first-line treatment for HER2 positive metastatic breast cancer.

Avastin for HER2 positive metastatic breast cancer

After the recent FDA decision to pull approval of Avastin for metastatic patients, there has been interest in identifying subsets of patients who may benefit from Avastin.

The phase III study (AVEREL) of Avastin (bevacizumab) in HER2 positive metastatic patients was similar in design to the Omnitarg study. 208 women were treated with Herceptin and Taxotere alone. 216 also received Avastin. The New York Times, Los Angeles Times and US News and World Report/HealthDay covered the study.

For the Avastin group, progression-free survival was 16.5 months, compared to 13.7 months for the 208 in the Herceptin/Taxotere only group.

But some question whether small benefits in progression-free survival are important.

According to the New York Times, "there was absolutely no difference in how long the women lived." Genentech has decided not to apply for FDA approval for HER2 positive breast cancer. A company representative noted, "Our bottom line is we do not believe that the difference in P.F.S. is of a sufficient magnitude that it is likely to gain regulatory approval."

Future research will attempt to identify the subset of patients who benefit from Avastin. As Dr. Gabriel Hortobagyi from MD Anderson noted in Los Angeles Times,

"I have no doubt that Avastin is a very powerful drug for some patients. . . The problem with Avastin is we don’t have a biomarker to help us identify the sub-group."

Afinitor for hormone-receptor positive metastatic breast cancer

A study (BOLERO-2) of Afinitor (everolimus) involving 704 women with hormone-receptor positive breast cancer which progressed on prior hormone therapy was covered by The New York Times, Los Angeles Times and Medical News Today. The study was published in The New England Journal of Medicine on December 7. (Link to full text.)

For women who took Afinitor plus the aromatase inhibitor Aromasin (exemestane), median progression-free survival was 7.4 months, compared to 3.2 months for women who took Aromasin alone.

However, the New York Times (Dec. 7) noted that because all women had already failed to benefit from hormone therapy, "perhaps it is not surprising that the control arm did not do that well on exemestane alone."

But, the trial researchers said that doctors often prescribe Aromasin in practice when other hormone therapies fail.

Medical News Today quoted Dr. Hortobagyi, a study coauthor, to say, "These findings may establish a new standard of care for advanced breast cancer."

Faslodex for hormone-receptor positive metastatic breast cancer

A phase III trial (SWOG S0226) of Faslodex (fulvestrant) plus Arimidex (anastrozole) for women with hormone-receptor positive metastatic breast cancer was covered by the Medical News Today on December 9.

In the study, 707 postmenopausal women were assigned to receive Arimidex plus Faslodex or Arimidex alone. Compared to the Arimidex alone arm, the Faslodex arm experienced longer median overall survival (47.7 months vs. 41.3 months) and longer progression-free survival (15 months vs. 13.5 months).

Both Arimidex and Faslodex are already used to treat breast cancer, though not in comination. The lead study coordinator noted that "these patients have not had a new treatment that gave them an overall survival benefit in more than a decade."

Entinostat for hormone-receptor positive metastatic breast cancer

A small phase II study (ENCORE 301) of entinostat for locally recurrent or metatstatic breast cancer was covered in a PR Newswire press release and the New York Times (Dec. 7)

In the study, 130 patients were treated with Aromasin (exemestane) alone or Aromasin plus entinostat. The median overall survival for the entinostat group was 26.9 months, compared to 19.8 months in the Aromasin alone group. Progression-free survival was also better with entinostat (4.3 months vs. 2.3 months.)

A randomized phase III study is anticipated to begin enrollment in the first half of 2012.

Abraxane as first-line treatment for metastatic breast cancer

A phase II study comparing Abraxane (nab-paclitaxel) to Taxotere (docetaxel) as first-line therapy for metastatic breast cancer was covered by Medical News Today on December 12.

In the study, 300 women who received no prior chemotherapy for metastatic disease were divided into four groups. Three groups received different doses of Abraxane. The fourth group received Taxotere.

The best median overall survival was achieved by the group that received 150 mg of Abraxane twice weekly (33.8 months.) The other two Abraxane dose schedules achieved median overall survival of 22.2 months and 27.7 months. For the Taxotere group, median overall survival was 26.6 months.

Progression-free survival was also better for the Abraxane 150mg/twice weekly group at 14.6 months, compared to 7.5 months and 10.9 months for the other Abraxane doses and 7.8 months for the Taxotere group.


We'll continue to follow research developments for women with metastatic breast cancer. We add links to media stories and journal abstracts to our website, LATESTBreastCancer.com everyday. The latest news and research may be explored anytime by clicking the Treatments tab.

BRCA Mutation Breast Cancer News: The 2011 San Antonio Breast Cancer Symposium and Beyond

Last week there were several headlines from the 2011 San Antonio Breast Cancer Symposium. Today, we'll share the stories relevant to women with BRCA 1/2 gene mutations and some recent studies not presented at the Symposium.

Links may be found on the BRCA 1/2 Gene Testing (General) page of our LATESTBreastCancer.com website.

The risk of cancer in the other breast

It is understood that women with BRCA mutations have a higher risk of developing breast cancer, but how do they do once diagnosed with breast cancer?

A study from the Netherlands found that women with breast cancer who carry a BRCA 1 or BRCA 2 gene mutation have a higher risk of developing cancer in the opposite breast than non-carriers. Medical News Today and MSN/HealthDay covered the Symposium presentation.

The study followed 5,061 women with cancer in one breast for about 8 years. 211 women carried a BRCA 1 or BRCA 2 gene mutation. For women with a BRCA mutation, the 10-year risk of developing cancer in the opposite breast was 17.6 percent, compared to a 6 percent risk for non-carriers.

Age at diagnosis affected risk. For BRCA carriers first diagnosed before the age of 40, the 10-year risk was 26 percent. For those diagnosed between 40 and 50, the risk was 11.6 percent.

Triple-negative status also mattered. Triple-negative BRCA carriers had a 10-year risk of 18.9 percent, compared to 11.2 percent for BRCA carriers who were not triple-negative.

In her blog from the Symposium, Dr. Susan Love noted,

Of note, most of the women in this study had not had their ovaries out, which decreases the risk of second cancers significantly (70%). The study also found that both chemotherapy and hormonal therapy for the first cancer seemed to reduce the chance of getting a second cancer in the other breast. In this era of bilateral mastectomies, it was a good reminder that the risk to the other breast is not the same in everyone.

The risk of metastasis and death

Not all BRCA news this month came from the conference. A December Reuters piece discussed a recent Journal of Clinical Oncology (Dec. 5) study which compared survival differences among BRCA 1 mutation carriers, BRCA 2 carriers and non-carriers with breast cancer. Over 3,000 women were included. 90 had BRCA 1 mutations and 70 had BRCA 2 mutations.

The study found no difference in risk of metastasis and death between non-carriers and those with BRCA 1 mutations.

On the other hand, women with BRCA 2 mutations had a significantly higher risk of metastasis and breast cancer death. This may be explained by the fact that BRCA 2 carriers had worse tumors at diagnosis. When compared to women with similar age, tumor stage, nodal status and hormone receptor status, there was no difference in risk.

For BRCA 2 carriers, risk of death could be reduced with standard breast cancer treatment. For BRCA 2 carriers who did not receive chemotherapy, the risk of death increased over 300 percent. According to the lead study author, quoted in Reuters Health, "A lot of these women with genetic predisposition may develop tumors that have poor characteristics. . . But if they get standard treatment available they seem to do OK."

The risk of cancer at an earlier age

One study presented at the Symposium asked if the source of a BRCA 1/2 mutation, from the carrier's father or mother, affected breast cancer risk. US News and World Report/HealthDay covered the study on December 8.

Interestingly, for women with BRCA 1 mutations, those who inherited it from their mother were on average 45 at diagnosis. Those with BRCA 1 mutations from their fathers were on average 38.

For women with maternal BRCA 2 mutations, the average age at diagnosis was 50, compared to 41 for those with paternal BRCA 2 mutations.

The lead researcher noted that if confirmed in larger studies, "doctors might think about watching and waiting in young women" with maternal BRCA mutations and "being more aggresive" in young women with paternal mutations.

The risk of cancer for non-carriers from a family of BRCA carriers

What about women who do not carry a BRCA mutation, but come from a family of carriers? Are they at increased risk?

A Journal of Clinical Oncology study from Stanford studied 3,047 families with this question in mind. 160 families had BRCA 1 mutations. 132 had BRCA 2 mutations. Reuters discussed the results on October 31.

The study found "no evidence of increased breast cancer risk" for non-carriers from BRCA families compared to women with first-degree relatives from non-BRCA families. The authors concluded, "These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation."

These are only the latest research developments for BRCA mutation carriers. At LATESTBreastCancer.com, we follow breast cancer news and research daily. We add links to our website, sorted by treatment type. You may explore any time by clicking the Treatments tab.

Tomorrow's blog will highlight the latest news from the San Antonio Breast Cancer Symposium for women with metastatic breast cancer. Please stay tuned.

Mastectomy or Lumpectomy Plus Radiation: The Latest (and Longest) Study

Women with breast cancer have two surgical options - mastectomy or lumpectomy plus radiation, also known as breast conserving surgery or breast conservation therapy.

Both have pros and cons, but which is better in terms of survival and recurrence?

Today we'll share the latest (and longest) study, a 25 year follow-up of the National Cancer Institute (NCI) Breast Conservation Trial. A link to the full-text of the study, published online in Breast Cancer Research and Treatment on November 24, may be found on the Breast Conserving Surgery page of our website.

Background: Six studies found similar survival outcomes

Six major trials have compared survival rates of the two surgical options. To date, all have found lumpectomy plus radiation to be an "accepted alternative" to mastectomy with "similar survival outcomes." (Links to the various study abstracts may be found in the References section at the end of the current study.)

In addition, a meta-analysis of all six trials conducted by the Early Breast Cancer Trialist Group Collaboration "confirmed the noninferiority of breast conservation therapy compared with mastectomy," despite differences in eligibility criteria and treatment technique between trials.

The current study is one of the original six. It shares data from a 25.7 year median follow-up. It is a relatively small study, but the longest reported follow-up to date.

The NCI study design

Between 1979 and 1987, 247 women with breast tumors measuring 5cm or less were randomized to receive either lumpectomy plus radiation or a mastectomy. All women were treated with chemotherapy (Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide)). After 1985, postmenopausal women with node-positive, estrogen-receptor positive breast cancer were also given tamoxifen for five years.

No difference in overall survival

Similar to the other five studies, the current NCI study demonstrated "no survival differences when comparing lumpectomy followed by whole breast irradiation versus mastectomy."

After 25 years, however, there was a "slight" survival advantage in the mastectomy group.

Predictors of decreased survival included patient age older than 50, left-sided tumors, tumor size greater than 2cm and more than 4 positive lymph nodes.

No difference in risk of metastasis

The study found "no significant difference in risk of distant metastasis" between the two arms.

High rate of recurrence in the same breast as the lumpectomy

Even though survival and metastasis rates were similar, the NCI study found a high rate of tumor recurrence in the breast treated with a lumpectomy. "More than 1 out of every 5 patients (22.3%)" in the lumpectomy group experienced a recurrence in the same breast requiring a salvage mastectomy.

The authors note that recent research suggests that same-breast recurrences may be a risk factor for decreased survival. However, in this study, even though 27 patients experienced a same-breast recurrence, there was no survival difference between the two groups.

There are several possible reasons why the rate of same-breast recurrence in this study may be greater than in the other studies.

First, the new tumor may actually be a new cancer, not a recurrence. In fact, there were 11 cancers in the opposite breast in the lumpectomy group and 15 in the mastectomy group, demonstrating that new cancers can develop over time.

In addition, the recurrence rate may be higher because this is a longer study. In fact, 3 of the recurrences occurred after a patient had been disease-free for 20 years.

Also, by design, the NCI study included women with larger tumors. The trials with lower same-breast recurrence rates included smaller-tumors and "more stringent margin evaluation." It may be that the patients in this study were already at a higher-risk of recurrence.

Long-term side effects of radiation therapy

As part of the discussion, the authors wondered if the long-term side effects of radiation might have affected survival in lumpectomy group.

A previous meta-analysis suggested "a 1.3% increase in non-breast cancer death in patients receiving radiotherapy after surgery." Although there were 5 more non-breast cancer deaths in the lumpectomy group, this trial was "not adequately powered to detect late differences in non-breast mortality."

However, left-sided cancer was "a significant predictor" of mortality. Radiation to the left-breast has been associated with cardiotoxicity in other studies. The NCI is currently conducting "extensive cardiac studies" of the 60 surviving patients in this trial.

The authors conclude that now that patients are living longer, minimizing treatment toxicity "has become a priority."

This is only the latest study on breast conserving surgery. For two-years of news and research on this and other treatment options, please visit our LATESTBreastCancer.com website. You may start exploring by clicking the Treatments tab.

As a final note, triple-negative breast cancer is a special situation. We discussed the latest research on mastectomies and lumpectomies plus radiation for triple-negative patients in our August 31 blog.

Alcohol and Breast Cancer: November News and Research

This month, there's been a lot of buzz (forgive the pun) about alcohol use and breast cancer. As the holidays approach, we thought it might be a good time to share the latest news and research. Links may be found on the alcoholic beverages page of our LATESTBreastCancer.com website.

The JAMA study: Even moderate drinking increases risk

The big story this month was a November 1 JAMA (Journal of the American Medical Association) study which followed over 100,000 nurses for almost 30 years. The New York Times, Los Angeles Times and Reuters covered the study.

According to the study, "Low levels of alcohol consumption were associated with a small increase in breast cancer risk." Greater consumption was associated with greater risk. The "most consistent measure" of risk was "cumulative alcohol intake throughout adult life."

The media attempted to sort out the details and put the findings in perspective.

All sources reported that moderate consumption (three to six drinks a week) was associated with a 15% increased risk. For women with a lifetime risk of 12%, three to six drinks a week would correlate with a 13.8% risk.

According to Reuters, the 10-year risk would be 2.8% for abstainers, 3.3% for three to six drinks a week and 3.5% for up to 13 drinks a week.

The Los Angeles Times further explained that women who consumed at least two drinks a day were 51% more likely to develop breast cancer than those who did not drink at all. Binge drinking (six or more drinks in one sitting) increased risk regardless of total consumption. Alcohol use between the ages of 18 and 40 was associated with increased risk, regardless of alcohol use after 40.

The New York Times highlighted some of the study limitations. First, the increase in risk associated with three to six drinks a week was "modest", and "for many women may not be enough to outweigh the heart-healthy benefits of drinking in moderation." Plus, "the new study was observational and lacked a control group, and it drew from self-reports, which can be unreliable."

The Los Angeles Times revisited the study and the balance between breast cancer risk and heart disease in a November 21 piece, "Women, the occasional drink, breast cancer and heart disease." In balancing the risks and benefits of drinking, the story was careful to note that any benefits associated with alcohol consumption relate to moderate, not heavy drinking.

The CANCER study: Alcohol and girls with a family history

Adults aren't the only ones who drink alcohol. How does adolescent alcohol consumption affect breast cancer risk?

A November 14 study in the journal Cancer examined the risk of benign breast disease, a "well-documented" breast cancer risk factor, among young women. A EurekAlert! press release covered the details.

The participants, aged 9 to 15 at the start of the study in 1996, completed periodic questionnaires until 2007 about family history of breast cancer and benign breast disease, alcohol use, height and weight.

The study found that young women with a family history of breast cancer or maternal history of benign breast disease had an increased risk of developing benign breast disease. Consuming seven alcoholic drinks a week doubled that already increased risk. The authors concluded, "Adolescents with family history may reduce their risk by avoiding alcohol."

Interestingly, among girls with no family history, the risk of benign breast disease was associated with other factors, such as weight, waist size and adult height. The authors note that this may possibly reflect different causes of breast cancer.

Alcoholics more likely to die of cancer

The JAMA study above addressed moderate alcohol use. On the other extreme, a November 15 US News and World Report/HealthDay story covered an Italian study of 2,300 alcoholics in Florence.

Compared to the general population, alcoholics were more likely to die from oral cancers, liver cancer, pancreatic cancer and breast cancer. They were also more likely to die from infections, diabetes, other diseases and violent crimes. Female alcoholics had higher survival rates than males, "possibly because women are more likely to get help for alcoholism."

The study author noted that the increased risk of death may be due to the effects of alcohol on human organs and lifestyle factors such as smoking, drug abuse, promiscuity and poor diet.

At LATESTBreastCancer.com, we follow breast cancer news and research daily. New studies and media stories are added to our website and database, sorted by topic. Topics include imaging, diagnostic testing, chemotherapy, radiation, targeted drugs, surgeries, complementary therapies and lifestyle options, such as alcohol use. We highlight the latest developments in this blog. However, topics may be explored on our website anytime. Simply click the Treatments tab to get started.

Our goal is to make internet research easy. Please stay tuned!

TRAM Flap and DIEP Flap Breast Reconstruction: The Latest Research on Side Effects and Complications

There are several options for breast reconstruction after a mastectomy. Some, such as the TRAM (transverse rectus abdominis myocutaneous) Flap and DIEP (deep inferior epigastric perforator) Flap procedures, use tissue from the abdomen to reconstruct the breast.

How does this affect the abdominal region? Are there any other potential complications?

A couple of recent studies and several recent news items have addressed the potential side effects and complications of TRAM Flap and DIEP Flap reconstruction. Links may be found on the TRAM Flap or DIEP Flap page of our website.

Potential abdominal side effects of TRAM Flap with muscle removal

Traditional TRAM Flap procedures remove a section of abdominal muscle. For some women, this may cause abdominal weakness and pain. On November 9, a CBS News affiliate in Minnesota published a video and story about two young mothers who suffer with abdominal pain and weakness after TRAM Flap procedures.

Dr. David Ruebeck, a plastic surgeon who was interviewed for the story, said that extreme side effects, such as those experienced by the women in the story are rare, but can happen. He noted that the benefits, such as a natural reconstruction from your own tissue and related tummy flattening, sound "really good," but have "some tradeoffs and some risks women have to be aware of."

He said it usually takes about a month to recover from a TRAM Flap procedure.

“The worst case scenario would be a situation where weakness or pain or bulging becomes a daily problem. A disability keeps a person from working or exercising the way they like of effecting posture or other comfort,” Dr. Ruebeck said. “That’s quite unusual. There’s not much that can be done about it.”

Potential abdominal side effects of muscle-sparing TRAM Flap and DIEP Flap

Whereas the original TRAM Flap procedure involves the removal of abdominal muscle, newer procedures, such as muscle-sparing TRAM Flap and the DIEP Flap surgeries attempt to spare the abdominal muscles. Even with these newer procedures, the risk of abdominal pain and weakness remains.

An October 21 study in the journal Cancer evaluated the quality of life of patients after muscle-sparing TRAM Flap and DIEP Flap procedures. Several media sources, such as US News and World Report/HealthDay, Medical News Today and the Canadian National Post covered the study.

On the positive side, the study found that gains in breast satisfaction, psychosocial and sexual well being were "clinically meaningful" as early as three weeks after surgery.

However, the authors noted that "these gains are accompanied by significant deterioration in physical well being of the abdominal donor site."

According to the National Post story, Dr. Toni Zhong, the study's lead author, "was surprised to find that even . . . in the most careful attempts to remove tissue without disturbing muscle, patients sometimes experienced muscle weakness or a bulge that persisted even three months after surgery."

She noted that the abdominal effects did not render the patients bed-ridden or inhibit everyday activities. She said, "“Some people are happy to put up with it and say it’s the price that I paid in order to have such a great breast reconstruction.” But "it can be a problem" for active women who notice the loss of muscle strength.

The study of 51 women collected satisfaction data up to three months post surgery. Dr. Zhong plans to evaluate abdominal function at six months and one year post surgery.

Tamoxifen use may cause complications in microvascular flap procedures

In a microvascular flap reconstruction, blood vessels and veins are cut and reattached using microsurgical techniques. The DIEP Flap procedure and a type of TRAM procedure called the TRAM Free Flap are microvascular procedures.

As with any surgery, microvascular flap procedures carry a risk of complications, such as ultimate flap loss.

An October 7 study from MD Anderson in Plastic and Reconstructive Surgery found that tamoxifen use "may increase the risk of microvascular flap complications." In the study, patients on tamoxifen has a "significantly increased rate of immediate total flap loss . . . and a lower rate of flap salvage. . ." The authors concluded that, "Surgeons should consider temporarily stopping the drug 28-days before microsurgical breast reconstruction."

These are only the most recent studies on TRAM Flap and DIEP Flap breast reconstruction. For two years of news and research, plus information on other reconstruction procedures, please visit our LATESTBreastCancer.com website. From the home page, click the treatments tab to explore the surgery section of our website.

Oncotype DX for Breast Cancer: October News and Research

The Oncotype DX Breast Cancer Assay has been the subject of several recent studies. Topics include how the Oncotype DX compares to and affects doctor assessment of risk, how it compares to other markers and how well it quantifies HER2 status. Today we'll highlight the seven most recent studies. Links may be found on the Oncotype DX page of our website.

A little background

The Oncotype DX Breast Cancer Assay is a test used to assess the risk of breast cancer recurrence in women with early-stage, estrogen-receptor positive, node-negative tumors. The Recurrence Score, which is calculated based on the expression of 21 genes, may help with the decision on whether to pursue chemotherapy. For example, patients with a very low risk of recurrence may decide that the small potential benefit from chemotherapy may not be worth the risk of side effects.

In addition to the Recurrence Score, the Oncotype DX report includes quantitative scores that reflect estrogen receptor (ER), progesterone receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER2) gene expression. This data may assist with decisions on whether to treat with hormonal therapy, such as tamoxifen, or anti-HER2 drugs, such as Herceptin.

Comparing Oncotype DX to doctors' assessment of risk

In a classic man versus machine match-up, two recent studies in The Oncologist explored how doctor assessment of risk compared to the Oncotype DX Recurrence Score and whether the Recurrence Score changes treatment decisions.

In the first, published online September 20, six academic oncologists predicted whether various pathological scenarios would receive low, intermediate or high Oncotype DX Recurrence Scores. As a whole, the oncologists were able to accurately predict the high risk scores, but were less able to distinguish between low and intermediate risk scenarios. In addition, when the actual Recurrence Scores were provided, treatment decisions changed in 19% of the cases. The authors noted that additional studies are needed to assess whether changes in treatment decisions affect outcomes.

In the second study, dated October 20, four surgeons, four medical oncologists and four pathologists estimated recurrence risk and made treatment recommendations for 154 patients based on pathology data. The medical professionals' estimations agreed with the Oncotype DX Score in 54% of the cases. The professionals tended to overestimate risk compared to the Recurrence Score. The authors concluded that the Recurrence Score "provides useful information that improves patient selection for chemotherapy and changes treatment recommendations in approximately 25% of cases."

How accurate is the Oncotype DX HER2 status score?

As mentioned above, in addition to the Recurrence Score, the Oncotype DX provides a score to quantify HER2 expression. An October 11 Journal of Clinical Oncology study found "an unacceptable false-negative rate" for HER2 status. TheDoctorsChannel.com published a video and story about the study on October 24.

The study used standard IHC and FISH HER2 testing to check the quality of the Oncotype DX HER2 status score for 843 patients. Of the 784 patients negative by IHC/FISH, 779 (99%) were also negative by Oncotype. However, all of the 23 patients deemed equivocal by IHC/FISH were classified as negative by Oncotype. Of the 36 positive by IHC/FISH, only 10 (28%) were classified as positive by Oncotype, 12 (33%) were reported as equivocal and 14 (39%) as negative.

The authors concluded that the high false-negative rate "could create confusion in the decision-making process for targeted treatment and potentially lead to mismanagement of patients with breast cancer if only GHI [Genomic Health] HER2 information is used."

How does IHC4 compare to Oncotype DX?

There's been some buzz in the UK about an alternative to the Oncotype DX. An October 19 article in The Telegraph (UK) discussed an IHC4 test, noting that it could be available in as little as a year, and "should cost a tenth" of the Oncotype DX in the UK.

What's the buzz about?

An October 11 study in the Journal of Clinical Oncology compared the Oncotype DX Recurrence Score to an IHC4 prognostic model, which used estrogen receptor (ER), progesterone receptor (PR), Ki-67 and HER2 status from standard IHC testing. IHC stands for 'Immunohistochemistry,' a very common (and inexpensive) test used to analyze the amounts of those four proteins in a biopsy sample.

In the study, all four IHC markers provided independent prognostic information. Combined in the IHC4 model, the information was similar to the Oncotype DX Recurrence Score, with "little additional prognostic value" seen by combining IHC4 and the Recurrence Score.

The study suggested that "the amount of prognostic information contained in four widely performed IHC assays is similar" to that in the Oncotype DX Recurrence Score. The authors noted that further studies are needed to "determine the general applicability of the IHC4."

In the UK, the National Institute for Health and Clinical Excellence (NICE) is reviewing several genetic risk assessment tests to make recommendations for the National Health System (NHS). The Oncotype DX and IHC4 are included, as well as the MammaPrint test, Breast Cancer Index and others. (Link to review protocol.)

How does Ki-67 expression compare to Oncotype DX?

Ki-67 expression is one of the 21 factors considered in the Oncotype DX Recurrence Score. An October 4 study in the British Journal of Cancer, noting that Ki-67 testing "is less expensive than Oncotype DX," compared the two values for 53 patients. The study found a "strong linear correlation" between the two scores. All patients with low Ki-67 were low to intermediate risk with Oncotype DX. All with high Ki-67 were high or intermediate with Oncotype DX. The authors concluded that Ki-67 status is a "major, but not the sole determinant of Oncotype Dx score."

Can additional data improve the Oncotype DX?

An October 17 Journal of Clinical Oncology study found that supplementing the Oncotype DX score with other factors such as tumor size and patient age "refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk." However, the additional information "did not seem to enhance the value" of the Recurrence Score in terms of predicting chemotherapy benefit.

Oncotype DX report format may be difficult to understand

Finally, an October 1 Breast Cancer Research and Treatment study asked if the current Oncotype DX report format is "a good approach for communicating results to patients." Compared to other sample reporting formats, the standard report was more difficult to understand and interpret. The authors suggest that a less complex report might be more effective in communicating test results to patients.

These are only the seven most recent studies on the Oncotype DX assay for breast cancer. For two years of news and research, plus general overviews, please check the Oncotype DX page of our LATESTBreastCancer.com website. From the home page, click the Treatments tab and search for 'Oncotype' in the search box on the top right of the page.

Femara for Breast Cancer: October News and Research

October has been hopping with news and research about the aromatase inhibitor Femara (letrozole) for breast cancer. Today we'll share the five latest studies and the headlines about them. Links may be found on the Femara (letrozole) page of our website.

Femara more effective than tamoxifen

The big story this month was an October 21 study in The Lancet Oncology which compared 8 year recurrence and survival rates for postmenopausal women taking Femara, tamoxifen or a sequential combination of both for early-stage, hormone-receptor positive breast cancer. The study is known as the Breast International Group (BIG) 1-98 study. The New York Times, The Telegraph (UK), US News and World Report/HealthDay and Medical News Today all ran stories.

According to the study, Femara alone resulted in a reduction in breast cancer recurrence and death compared to tamoxifen alone. Sequential use of tamoxifen and Femara, in any order, did not improve outcome compared to Femara alone, "but might be useful strategies when considering an individual patient's risk of recurrence and treatment tolerability."

Femara improves response to chemotherapy before surgery

Not all of the October Femara studies made headlines. An October 16 study in Breast Cancer Research and Treatment evaluated the addition of Femara to chemotherapy before surgery for postmenopausal women with locally advanced breast cancer. For women with hormone-receptor positive breast cancer, the addition of Femara to chemotherapy improved clinical and pathological response rates with "acceptable toxicity" compared to chemotherapy alone.

Femara reduces bone mineral density

Not all Femara news this month was good. An October 14 Annals of Oncology study evaluated bone loss in women in the BIG 1-98 study discussed above. It found that Femara use was associated with a reduction in bone mineral density, whether used alone or in sequence with tamoxifen, when compared to the use of tamoxifen alone. In fact, the "sequential schedules were as detrimental for bone density" as taking Femara alone.

Zometa improves bone mineral density for women taking Femara

There may be a way to reduce the risk of bone loss associated with Femara. An October 10 study in the journal Cancer compared the immediate use of Zometa (zoledronic acid) with the delayed use in postmenopausal women with early breast cancer taking Femara for 5 years. The trial is known as Z-FAST. The Los Angeles Times and Medical News Today covered the study.

According to the study, taking Zometa (zoledronic acid) with Femara "upfront," from the beginning, "significantly and progressively" increases bone mineral density, compared with a delayed start of Zometa. The authors also found that "long-term coadministration of letrozole and zoledronic acid is well tolerated."

Another study evaluated the data from the Z-FAST trial. Whereas the October 10 Cancer study looked at bone mineral density at 5 years, an October 17 study in Clinical Breast Cancer evaluated the data at month 12. It also found that immediate use of Zometa prevented bone loss and increased bone mineral density, "regardless of BMD [bone mineral density] at baseline."

These are only the five most recent studies on Femara (letrozole) for breast cancer. For two years of news and research, plus overviews and FDA information, please check the Femara (letrozole) page of our LATESTBreastCancer.com website. From the home page, click the Treatments tab and search for 'Femara' in the search box on the top right of the page.

We'll continue to follow developments in breast cancer research. Links are added to our website daily and interesting findings are highlighted here. Please stay tuned.

Vitamin Use After Breast Cancer Diagnosis: Antioxidant Safety

Is it safe to take antioxidants during breast cancer treatment? According to a recent study in the journal Cancer, the answer may depend on the type of supplement and the dose.

The study

The study examined the association between antioxidant use and breast cancer recurrence and survival in 2,264 women with early-stage breast cancer. 81% took antioxidants after diagnosis, either individually or in multivitamin form. (Links to the study and Reuters and Indianapolis Star articles may be found on the multivitamin page of our website.)

Vitamin C and vitamin E

Taking single supplements of vitamin C or vitamin E six or seven times a week was associated with a lower risk of breast cancer recurrence. Vitamin E was also associated with a decreased risk of death from any cause.

However, the lead researcher noted that much of this benefit may be due to a "healthy user bias," meaning women who take supplements "tend to have healthier habits in general."

Carotenoids: Vitamin A, beta-carotene and lutein

On the other hand, "frequent use" of any combination of carotenoids, such as vitamin A, beta-carotene and lutein, was associated with an increased risk of death from breast cancer or any other cause. Of 89 women who took carotenoids six to seven days a week, 18 percent died of breast cancer, compared to less than 7% of women who did not.

Because these patients would also have a "healthy user bias," the lead researcher noted the findings on the increased risk of death "are even more striking."

Multivitamins

The study findings did not pertain to multivitamin use, which "generally have more moderate doses of individual nutrients."

Notes of caution from the researchers

Heather Greenlee, lead researcher, told Reuters that the study "adds to the growing body of literature suggesting that dietary supplements containing high doses carotenoids may be harmful, and people should think twice before taking them."

At LATESTBreastCancer.com, we follow breast cancer news and research daily. We highlight interesting developments in this blog and add links to medical journal abstracts and news articles to the treatment pages of our website. We sort news and research by test, treatment option and complementary therapy. Our goal is to make internet research easy. We look forward to keeping you posted.

Herceptin Plus Chemotherapy for HER2 Positive Breast Cancer: The Latest Data in the Hunt for the Best Combination

Herceptin (trastuzumab) is the treatment of choice for women with HER2 positive breast cancer. By itself, it is associated with a risk of heart damage. What happens when it is combined with chemotherapy? Which drug combinations are best in terms of effectiveness and side-effects?

Today we'll share the two most recent studies on Herceptin in combination with chemotherapy. Both evaluated chemotherapy combinations with and without anthracyclines, such as Adriamycin and Ellence. Links may be found on the Herceptin (trastuzumab) page of our website.

TCH better than AC-T plus H as adjuvant therapy

An October 6 study in The New England Journal of Medicine evaluated the risks and benefits of Herceptin plus chemotherapy as adjuvant (after surgery) therapy for women with early-stage, HER2 positive breast cancer. The Los Angeles Times and US News and World Report/HealthDay covered the study.

The 3,222 women in the study were divided into three groups. One received Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide) followed by Taxotere (docetaxel) (AC-T). One received AC-T plus 52 weeks of Herceptin (AC-T plus H). The last received Taxotere, Paraplatin (carbobplatin) and 52 weeks of Herceptin (TCH).

In terms of effectiveness, the AC-T plus H and TCH groups had similar disease-free and overall survival rates, and both were superior to the group that did not receive Herceptin.

In terms of side-effects, the AC-T plus H group experienced "significantly higher" rates of congestive heart failure and cardiac dysfunction than the TCH group. There were seven cases of leukemia in the AC-T plus H group and one in the TCH group.

The authors concluded that the addition of one year of Hercpetin significantly improved disease-free and overall survival. The risk-benefit ratio favored the TCH combination over AC-T plus H, "given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia."

PH-FECH better than TCH as neoadjuvant therapy

A September 27 study in Cancer evaluated Herceptin plus chemotherapy as neoadjuvant (before surgery) treatment. This time, TCH came out on the bottom.

The 300 HER2 positive women were treated with either Taxol (paclitaxel) and Herceptin followed by 5-FU, Ellence (epirubicin), Cytoxan and Herceptin (PH-FECH) or Taxotere, Paraplatin and Herceptin (TCH).

Patients in the PH-FECH group experienced a higher rate of pathological complete response (pCR), meaning tumor disappearance. They also had a lower risk of recurrence and death compared to the TCH group.

In terms of side-effects, there was "no significant difference" in heart damage. However, the authors noted that the women in the PH-FECH group had "fewer cardiac comorbidities at baseline," meaning they had a lower risk of heart damage when the study started.

The authors concluded that the type of neoadjuvant therapy is predictive of pCR rate. "Although TCH is active, PH-FECH shows a higher pCR rate and RFS [relapse-free survival] advantage."

At LATESTBreastCancer.com, we'll continue to monitor research on Herceptin plus chemotherapy. Today's studies are only the two most recent. For two-years worth of news and research, please visit the Herceptin page under the Treatments tab of our website.

Nausea and Vomiting after Chemotherapy for Breast Cancer: New ASCO Guidelines on Prevention

Nausea and vomiting are perhaps the most unpleasant potential side effects of chemotherapy for breast cancer. Last week the American Society of Clinical Oncology (ASCO) updated its practice guidelines for the prevention of nausea and vomiting. Today, we'll highlight the latest recommendations.

Links to the new guidelines published in the Journal of Clinical Oncology, a DoctorsChannel.com video about the update and a Los Angeles Times story on the start of preventative medication may be found on the Aloxi (palonosetron) page of our website.

Adriamycin/Cytoxan and Ellence/Cytoxan combinations have a high risk

The ASCO guidelines classify chemotherapy drugs and combinations according to the likelihood that they may cause nausea and vomiting. Individually, Adriamycin (doxorubicin), Ellence (epirubicin) and lower dose Cytoxan (cyclophosphamide) are considered to have a moderate risk of causing nausea and vomiting. Under the new guidelines, the Adriamycin/Cytoxan and Ellence/Cytoxan combinations are considered to have a high risk, meaning they are very likely to cause nausea and vomiting.

Three drug combination for chemotherapy with a high risk

For chemotherapy drugs with a high risk of causing nausea and vomiting, such as the combinations above, Platinol (cisplatin) and high dose Cytoxan, the guidelines recommend a three drug combination:

EMEND (aprepitant) or EMEND for Injection (fosaprepitant) . Because EMEND for Injection is administered for 1 day rather than 3, it may be preferable.

plus

Aloxi (palonosetron). If Aloxi is not available, Kytril (granisetron) or Zofran (odansetron) may be substituted.

plus

dexamthasone.

Two drug combination for chemotherapy with a moderate risk

For chemotherapy with a moderate risk of causing nausea and vomiting, such as Camptosar (irinotecan), Paraplatin (carboplatin) or Adriamycin, Ellence or low dose Cytoxan alone, the ASCO recommends a two drug combination of dexamethasone plus Aloxi. The report notes that there is "moderate evidence" suggesting that EMEND may add benefit.

One drug for chemotherapy with a low risk

For chemotherapy with a low risk of causing nausea and vomiting, such as Taxotere (docetaxel), 5-FU (fluorouracil), Gemzar (Gemcitabine), methotrexate, Torisel (temsirolimus) and Ixempra (ixabepilone), the ASCO recommends a single dose of dexamethasone.

According to an October 3 article in the Los Angeles Times, it's not unusual to start taking medication to prevent nausea before the start of chemo.

A September 26 What to Know guide from ASCO provides a patient-friendly summary of the ASCO guidelines, including a classification of chemotherapy drugs by risk of nausea and vomiting.

At LATESTBreastCancer.com, we'll continue to follow research on the prevention of nausea and vomiting related to chemotherapy for breast cancer. Any new developments will be added to the treatment pages of our website and highlighted here. Please stay tuned.

Zometa for Early-Stage Breast Cancer: Hormones May Matter

Can Zometa (zoledronic acid) prevent recurrence in women with early-stage breast cancer? Today we'll share the latest news and research. Links may be found on the Zometa (zoledronic acid) page of our website.

A new role for Zometa

Zometa is a bisphosphonate often prescribed to prevent bone loss in women taking aromatase inhibitors for breast cancer. It's also used to treat bone metastases in women with stage IV breast cancer.

Recent studies suggest Zometa may also prevent recurrence in women with early-stage breast cancer, but the results have been inconsistent. A new study in the New England Journal of Medicine suggests the key may lie in the hormonal status of the patient.

June: Zometa benefits premenopausal women on Zoladex and hormone therapy

A June 3 study in The Lancet Oncology evaluated Zometa in premenopausal women with hormone-receptor positive, stage I or II breast cancer, who were taking Zoladex (goserelin) for ovarian supression. (Drugs.com covered the study on June 3.)

About half of the 1,803 women took Zometa plus tamoxifen or Arimidex (anastrozole). The rest took tamoxifen or Arimidex alone.

At about 5 years follow-up, more than 2 years after completion of treatment with Zometa, 8% (76/900) of the Zometa group experienced a recurrence, compared to 12% (110/903) of the tamoxifen or Arimidex alone group. There was no significant difference in overall survival. (30 deaths out of 900 women taking Zometa, 43 out of 903 not taking Zometa.)

The authors concluded that the addition of Zometa "improved disease-free survival in the patients taking anastrozole or tamoxifen." They added, "These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer."

September: Zometa may only benefit postmenopausal women

In a September 25 New England Journal of Medicine study, about half of the 3,360 women with early-stage breast cancer were treated with Zometa plus standard chemo and hormone therapy. The rest received standard therapy alone. Patients varied in age, menopausal and hormone-receptor status.

In contrast to the Lancet study, at 5 years follow-up, the New England Journal of Medicine study found "no improvement" in disease-free survival for women with early-stage breast cancer taking Zometa. The authors concluded that their findings, "do not support the routine use of zoledronic acid as adjuvant therapy in unselected patients with early-stage breast cancer."

However, when the study participants were evaluated by subgroup, Zometa seemed to benefit postmenopausal women. (Reuters and Medical News Today covered this aspect of the study on September 25.) Zometa improved both disease-free survival (recurrence) rates and overall survival (death) rates for the group who had undergone menopause more than 5 years earlier.

The authors concluded, "For postmenopausal women, the use of bisphosphonates remains appropriate for the prevention of treatment-induced bone loss and osteoporosis and might have beneficial effects on disease outcomes. The optimum schedule, duration, and type of bisphosphonate therapy remain unknown."

Hormonal status may be the key

How do we reconcile these two studies? One found a benefit for premenopausal patients, the other did not. The answer may lie in the hormonal status of the patients.

The New England Journal of Medicine study noted that from a hormonal perspective, the postmenopausal patients in its study were similar to the premenopausal patients in the Lancet study who were treated with Zoladex for ovarian suppression. Both groups "had low levels of reproductive hormones at study entry." The authors suggest that Zometa "operates differently according to menopausal status."

Finally, the authors note that even though chemotherapy may induce menopause in young women, complete ovarian suppression may take "many months." They conclude, "Further investigation into the possible interaction between zoledronic acid and reproductive hormones is required."

At LATESTBreastCancer.com, we'll continue to follow developments in research on Zometa for breast cancer. We'll keep you posted.

Help for Women with Dense Breasts: U-Systems' somo-v Automated Breast Ultrasound (ABUS)

The movement toward enhanced breast screening for women with dense breast tissue is gaining momentum. Today's blog is meant to help these women advocate for a specific supplemental screening option: automated breast ultrasound. We'll focus on the somo-v ABUS system from U-Systems. I'll use a Q&A format.

First, how does Automated Breast Ultrasound (ABUS) differ from regular ultrasound?
Both use sound waves to detect abnormal structures in the breast that could be tumors. With plain vanilla ultrasound (hand-held ultrasound, or HHUS) either a radiologist or a highly-trained technician called a sonographer moves a kind of wand ("transducer") over the surface of the breast. Think of the wand like a flashlight. As the she moves the wand, she looks at the image on a monitor in real-time, trying to see possible tumors. Images can also be captured for later viewing.  With ABUS are that a much larger transducer is configured over the breast (it isn't manually moved over the breast), automatically taking different ultrasound images from different angles. These are then processed by a computer to construct a 3-D image.

What are the main advantages of ABUS?
First, the 3-D image gives a more complete picture of the entire breast than HHUS. Second, the images can be compared from year to year, or between visits, so any changes in the breast are easier to detect. Finally, the method doesn't require a diagnostic medical sonographer to perform. The imaging is automated, similar to mammography. So you don;t have to worry about whether or not the technician might be less experienced. Most ultrasound sonographers are trained and accredited. But their level of experience can also matter with HHUS.   

What systems are out there?
The main system on the market is called (and this is a mouthful...) the somo-v INSIGHT Automated Breast Ultrasound (ABUS) system.  It was developed by U-Systems, a Silicon Valley company that pioneered the field. A similar competing system called the ACUSON S2000 Automated Breast Volume Scanner (ABVS) is marketed by the large German company Seimens AG.

Can Automated Breast Ultrasound be used for screening?
The simple answer is "Yes, and it increasingly is." But realize that breast ultrasound, automated or not, is usually performed as a diagnostic procedure to further characterize a suspicious mammogram or MRI result. It's also commonly used to help surgeons guide needles when they perform biopsies.  Ultrasound is not traditionally used for screening to assess women with no suspicion of disease. However, given the growing concerns about mammography and women with dense breast tissue, ultrasound is increasingly used as a second, supplemental screening method for that subgroup of women. Generally, screening methods need to be more automated and require less technical skill than diagnostic methods, simply because more tests have to be performed more rapidly.  This is part of the appeal of the ABUS system.  But read on...

Is ABUS approved as a screening method in the US?
No. It's approved for diagnosis, but not for screening. That doesn't keep physicians from using it as a screening method. It does keep U-Systems from marketing it for screening. U-systems is conducting a very large study (20,000 women with dense breasts) in the United States to gain approval for screening. The study is looking at whether screening with mammography plus ABUS outperforms mammography alone.  Here we're talking about traditional 2-D mammography and not 3-D mammography (tomosynthesis). Enrollment continues, but the company already feels the data are strong and so they submitted an application to the FDA in April 2011. They added to the data a few weeks ago. The FDA could decide any day now.

Is ABUS approved as a screening method outside the US?
Yes, in Canada and in Europe. It was approved as a screening method by the Canadian regulatory agency Health Canada just last month (Aug 2011). Here's the announcement. It was granted European Union marketing approval a year ago (Sept 2010). Here's some info on that.

Is there a way I can see how it works?
The somo-v system was recently featured on Dr. Oz. Their site has three videos of that episode, which is all about supplemental breast screening. Watch all three if you have time.  If you just want to see the somo-v system, just watch part 2. Once you get there, you'll see the links to parts 1 and 3. Sorry but they're going to subject you to some commercials...

How much does it cost? 
That depends on the facility providing the service, but typically about $250-300.

Will it be covered by insurance?
That also depends on the judgment and policy of the facility you use, but often it's reimbursed.

How can I find a doctor that performs ABUS in my area?
First, you might check to see if you can get access through U-Systems' clinical study. Data from the trial have already been submitted, but they might still be recruiting. Outside of the clinical trial, it might take you a lot of time to call breast centers on your own. I'd probably just call the company (1-866-364-6777). Legally, remember, they can't talk about the system for screening. So just ask where there's a system installed in your area and hold the screening questions for the facility. Let's just call it "don't ask, don't tell!"


Where can I find more information?
Go to the somo-v Automated Breast Ultrasound page on the LATESTBreastCancer.com website. There we list web links to high-quality news articles and medical journal abstracts about every new medical option.

Afinitor, T-DM1 and Xeloda for Metastatic Breast Cancer

Today we'll share the latest news and research on Afinitor, T-DM1 and Xeloda for metastatic breast cancer.

Afinitor plus Aromasin (phase III)

The big story this week was a phase III trial of Afinitor (everolimus) plus Aromasin (exemestane) for post-menopausal women with advanced breast cancer presented at the 2011 European Multidisciplinary Cancer Congress (EMCC). Links to the EurekAlert!, Reuters and Bloomberg articles may be found on the Afinitor page of our website.

The trial, known as BOLERO 2, involved 724 hormone-receptor positive women whose cancer had become resistant to the aromatase inhibitors Femara (letrozole) or Arimidex (anastrazole). 485 received Afinitor plus Aromasin. 239 received Aromasin alone. Progression-free survival was almost 11 months in the Afinitor group, compared to about 4 months in the Aromasin alone group.

Afinitor is also being studied in combination with other drugs for advanced breast cancer. Novartis plans to file worldwide regulatory submissions for the Afinitor/Aromasin combination by the end of 2011.

TDM-1 (phase II)

Another EMCC presentation made headlines this week. The phase II study, TDM4450g, of trastuzumab emtansine (T-DM1) as first-line therapy in women with advanced HER2 positive breast cancer was covered by Medical News Today, Bloomberg and The Telegraph (UK).

The 137 patients were treated with either T-DM1 alone or Herceptin (trastuzumab) plus Taxotere (docetaxel). The median progression-free survival was 14.2 months with T-DM1 compared to 9.2 months with Herceptin plus Taxotere. In addition, the T-DM1 group suffered fewer side effects with less hair loss and hospitalization.

Larger, phase III trials are needed before regulatory approval. Last week, The Seattle Times shared an interesting story about Jeanne Sather, a breast cancer blogger whose efforts led to a geographic expansion of a T-DM1 trial. The story may be found on our T-DM1 page.

Navelbine/Gemzar vs. Xeloda alone (phase III)

Not all research on metastatic breast cancer involves brand new drugs. Some studies experiment with combinations of existing drugs.

A September 21 phase III study from Greece in the Annals of Oncology compared Navelbine (vinorelbine) plus Gemzar (gemcitabine) to oral Xeloda (capecitabine) alone for women with metastatic breast cancer previously treated with anthracyclines and taxanes.

Progression-free survival, overall survival and overall response were similar for both groups. The authors concluded, "Given the favorable toxicity and convenience of oral administration, single-agent capecitabine is recommended for compliant patients."

At LATESTBreastCancer.com, we'll continue to follow research on treatments for metastatic breast cancer. New developments will be added to our website and database and highlighted here. Please stay tuned.

The Latest Research on Breast Reconstruction after Mastectomy

Today we'll share the latest news and research on breast reconstruction after mastectomy. Topics include the reconstruction decision, the safety of silicone and a study on two-stage implants. Links to the news items and studies below may be found on the breast implant (with expander, two-stage) page of our website.

The decision to pursue reconstruction

Women facing breast cancer have many decisions to make about treatment. If a mastectomy is selected, additional decisions about breast reconstruction are required.

Reconstruction is not for everyone. According to a September 23 article in The Atlantic, women consider many factors such as cost, convenience and lifestyle. For women who decide against reconstruction, a variety of removable prosthetic breasts are available.

For those who choose reconstruction, there are many options, including saline and silicone implants and tissue grafting procedures such as TRAM flap, DIEP free flap and Gluteal free flap procedures.

Unfortunately, not everyone may be aware of their options. The Atlantic story noted that "the data suggest that only three in seven women get the chance to learn about reconstruction before they begin cancer treatment."

Moreover, uninsured women may never be informed of their reconstruction options. In a recent study, 52% of the 54 uninsured women "knew nothing about breast reconstruction." After learning about their options, the percentage who chose reconstruction rose from 47 to 76 percent (link).

FDA update on the safety of silicone implants

For those who choose silicone breast implants, there have been some concerns about safety. Back in June, the FDA issued an Update on the Safety of Silicone Gel-Filled Breast Implants. It was big news at the time, with the Los Angeles Times, The Washington Post, MedPage Today and Medical News Today covering the story.

Essentially, the FDA reviewed the latest studies and concluded that "silicone gel-filled breast implants have a reasonable assurance of safety and effectiveness when used as labeled." It found "no apparent association" between the implants and breast cancer, connective tissue disease or infertility.
Importantly, the FDA noted that 40 to 70 percent of breast reconstruction patients will need an additional surgery to modify, remove or replace the implant within the first 8 to 10 years. It recommended lifetime monitoring with periodic MRIs to detect asymptomatic ruptures.

The latest study on two-stage breast reconstruction

Breast implant reconstruction may be implemented in one or two stages. With one-stage, the implants are inserted immediately after the mastectomy. With two-stage, tissue expanders are inserted after the mastectomy, and replaced with permanent implant sometime later.

The latest study on two-stage breast reconstruction was published online in the American Cancer Society journal Cancer on September 14.

The study followed 151 women with stage II or III breast cancer for about 7 years. All received a skin-sparing mastectomy and axillary lymph node dissection with the placement of a tissue expander. All were treated with chemotherapy. About 4 weeks after chemo, tissue expanders were replaced with saline or silicone permanent implants. 8 weeks after the completion of chemo, post-mastectomy radiation was initiated.

At 7 years, local and regional control was 100%. Two women experienced chest-wall recurrence, but after 7 years. 29 patients experienced a distant metastasis. The 7-year distant metastasis-free survival rate was 81% and overall survival rate was 93%.

At 7 years, 29% underwent permanent implant removal or replacement (17.1% removal and 13.3% replacement.) The authors noted that it is "important" to consider this rate in the "context of the longevity of implants." They note,

"Breast prostheses are not permanent devices and may require revision over the life course of patients, even in women who receive implants primarily for augmentation purposes."

The study was unable to identify any factors, including implant type, which predicted a risk of implant replacement or removal.

The authors noted several limitations to their study. First, surgeries to modify the implants due to complications were not considered, but could be important as they they can "impact cost and quality of life." Also, the women in the study were treated at a single cancer center, Memorial Sloan-Kettering. The results "may not be generalizable to other populations at large."

At LATESTBreastCancer.com, we'll continue to follow the research in the field of breast reconstruction. Developments will be added to our website and database and highlighted here. Please stay tuned.

Dense Breast Tissue: Supplemental Screening Methods

For women who know they have dense breast tissue, we wanted to quickly list the screening methods that are currently used to supplement standard 2-D mammography. By clicking any link below you can quickly see the most recent news and medical journal articles on each.  To learn more by accessing complete lists of news and journal article links going back 2-3 years, go to LATESTBreastCancer.com and then find that screening method's page.

Breast ultrasound (US)
Ultrasound uses sound waves rather than x-rays (like mammography) to identify structures in the breast that could be tumors. Most ultrasound devices are hand-held. On our breast ultrasound page you'll find every recent news article and medical journal abstract on the use of breast ultrasound for the detection of tumors in dense breast tissue. Advantages of US are that it's relatively inexpensive (usually a few hundred dollars), widely available and doesn't cause discomfort. Hand-held ultrasound, though, requires a skilled practitioner and it will result in more false positives than mammography.

Automated breast ultrasound (ABUS)
The main advantage of automated compared to hand-held ultrasound is that enables a less labor intensive, operator-dependent workflow. The main (only?) system being marketed in the United States is the somo-v INSIGHT by U-Systems (Sunnyvale, CA). It has regulatory clearance as an adjunct to mammography and is seeing more use, particularly in Connecticut and Texas, states that recently passed dense breast tissue laws and that therefore are seeing increased demand for ultrasound screening.

3-D Mammography
Also called breast tomosynthesis and stereo digital mammography (SDM). The only FDA-approved system on the market in the United States is the Selenia Dimensions System by Hologic, Inc. (Bedford, MA). It was approved in February of this year and is becoming more available. In 3-D mammography, an x-ray imager moves around the breast, taking 15 images from different angles (standard mammography takes two images). These 15 images are then assembled using software to create the 3-D depiction. Imaging from different angles decreases the odds that a tumor will be completely hidden by dense breast tissue. I recommend the August 14th news story from the Boston Globe. The link is on LATESTBreastCancer.com's 3-D Mammography page. All links are conveniently listed in reverse chronological order.

Breast MRI
Along with breast ultrasound, breast MRI is the most commonly mentioned supplemental screening method for women with dense breast tissue. MRI uses a strong magnetic field to excite nuclear particles in breast tissue. A contrast agent chemical (gadolinium-DPA) is first injected into the bloodstream. This agent helps visualize areas containing blood vessel networks, which are suggestive of a tumor. MRI is highly sensitive but does generate a high rate of false positives. It is also very expensive ($2000-6000). The most recent news articles and medical journal articles on breast MRI can be found on our Breast MRI page. Among those are articles that discuss its use as a supplemental screening method for women at high risk, including women with dense breast tissue.

Molecular breast imaging (MBI) systems
Molecular breast imaging is "functional" imaging. It looks at metabolic activity in the breast tissue. This makes is complementary to "anatomical" imaging methods like mammography and ultrasound that look at tissue structures. MBI methods include BSGI (Breast-specific gamma imaging) and PEM (Positron emission mammography). Both generate fewer false-positives than breast MRI and so results in fewer unnecessary biopsies. They are also less expensive than MRI. BSGI and PEM are based on the same principle but use different radioactive tracer molecules and imaging systems. In both, the tracer is absorbed by cells throughout the body. Cancer cells, due to their increased rate of metabolic activity, absorb a greater amount than healthy cells and so appear as dark "hot spots" on the image. The major problem with MBI is that it  results in greater exposure to radioactivity.

The Latest Research on CYP2D6 Variations for Women on Tamoxifen

Do CYP2D6 variations matter for women on tamoxifen? Variations may affect how women metabolize tamoxifen, but do they make a difference in breast cancer recurrence or prevention? Recent studies suggest maybe not. Today we'll share the latest news and research on how CYP2D6 variations affect women on tamoxifen.

Background from the Dr. Susan Love Research Foundation

An overview from the Dr. Susan Love Research Foundation provides a nice background to the issue. Essentially, a gene called cytochrome P450 2D6 generates an enzyme called CYP2D6. Variations in the gene affect the enzyme production and affect how well a woman metabolizes, or processes tamoxifen. Some women process it better than others.

A 2007 study suggested that women with a certain variation were almost twice as likely to have their cancer recur. Subsequently, some specialists started recommending CYP2D6 testing before starting tamoxifen.

Later studies, however, found that variations in CYP2D6 made no difference in breast cancer recurrence. Dr. Love's website notes that more studies are needed to resolve the inconsistency in the research.

The Latest Research

Dr. Love's website was updated in January 2011. What has happened since then? Studies on CYP2D6 and tamoxifen continue to trickle in. Today we'll share the latest research. Links to all of the studies discussed below may be found on the CYP2D6 testing page of our website.

CYP2D6 variations when tamoxifen is prescribed for prevention

Tamoxifen is sometimes prescribed to prevent breast cancer in women at high-risk. An August 31 study in Clinical Cancer Research found that CYP2D6 variations made no difference in whether or not tamoxifen or Evista (raloxifene) were effective when taken to prevent breast cancer.

CYP2D6 variations when tamoxifen is prescribed to prevent recurrence.

Tamoxifen is also prescribed to prevent recurrence in women treated for breast cancer. Since January 2011, three studies have suggested that CYP2D6 variations make no difference in breast cancer recurrence rates for women on tamoxifen.

A January 15 study in the Journal of the National Cancer Institute from Denmark found, "The association between CYP2D6 inhibition and recurrence in tamoxifen-treated patients is likely null or small."

In a March 25 study in Breast Cancer Research and Treatment from Korea, CYP2D6 variations were not associated with clinical outcomes, such as recurrence, in early-stage breast cancer patients treated with tamoxifen.

Most recently, an August 5 MD Anderson study in Cancer found "no significant effect of CYP2D6 genotype on risk of recurrence in breast cancer patients who received adjuvant tamoxifen therapy."

Current Recommendations

Due to the current state of research, the 2011 National Comprehensive Cancer Network (NCCN) Guidelines do recommend CY2D6 testing for evaluating treatment with tamoxifen. (See March 21 OncLive.com article.)

In Europe, according to the 2011 St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer, "The Panel was almost unanimous in rejecting CYP2D6 testing to dictate choice of endocrine therapy type." In the UK, a cost/benefit analysis in the September issue of Health Technology Assessment concluded that CYP2D6 testing could not be recommended at this time due to the rapidly evolving research and limited and conflicting data.


At LATESTBreastCancer.com, we'll continue to follow the research in CYP2D6 testing and tamoxifen. We'll add any developments to our website and database and highlight them in this blog. Please stay tuned.

The Golden State's Dense Breast Tissue Bill: An Argument In Favor

Today I'll continue the discussion on California's dense breast tissue bill, SB 791, sponsored by Joe Simitian of Latest Medical's hometown of Palo Alto. The bill is similar to bills recently passed in Connecticut and Texas. Basically, it would require physicians to notify patients with highly dense breasts about their breast density and the possibility that they may require additional imaging services like ultrasound or MRI. The California Medical Association (CMA) and many physicians oppose the bill. Patients and patient advocates tend to support it. 

As the founder of a company focused on empowering cancer patients with information, I support the bill. To me, nothing justifies withholding potentially life-saving information from patients.

The simple, central issue is that today most women are not being informed about a serious health risk: dense breast tissue. According to a recent poll, 95 percent of women ages 40+ don’t know their breast density and close to 90 percent don’t know it increases the risk of developing breast cancer.  Yet the medical community has known about this issue for over a decade.

What are the arguments against the bill? I’ll use the CMA as a proxy for the opposition. In their press release, the CMA states that there isn't yet clarity on what "dense breasts" means, nor on what should be done clinically with the information. But "clarity" is a vague term. In fact, there's well over a decade of research about the risks associated with dense breast tissue and on the value of supplemental screening. It’s common sense that imaging the breast using different, proven methods will increase the likelihood of finding an abnormality. But we don't have to rely on common sense. Recent studies published in high quality medical journals come to the same conclusion.

In fact, as an argument against the bill, the CMA's press release says that breast density is already reported to physicians in mammography reports. Isn't this an admission that there is a workable way to measure breast density and that the information has clinical relevance?

One can concede that the measurement of breast density is an ongoing area of research. And one can concede that the value of different supplemental screening methods is still being quantified. The CMA's policy statement says that, "the science is still out on this matter." Yes, science is never finished. It's always still out on every matter.

Another CMA argument cites the bill's impact on patients (they'll be scared) and physicians (they'll face practical and legal problems). Possibly.  But these are secondary issues--consequences of communicating the facts. The truth can't be sacrificed for the sake of convenience. The priority must be patients' health, not shielding them from worry or protecting physicians.

Finally, one can argue that what's needed is better cost-benefit data regarding supplemental screening of women with dense breast tissue. But the bill doesn't involve changes to reimbursement. Maybe it should. But right now it's only about communicating information. Once they're informed, women can do their own cost-benefit analysis with their doctor. They can weigh in their other risk factors, their anxiety level about developing breast cancer, their level of concern about a possible unnecessary biopsy, and their ability to pay for supplemental screening if it isn't covered. This is a decision that women need to have the opportunity to make. The bill ensures that they will.

Without the notice that the bill requires, we know that many women with very dense breasts who aren't aware of this issue will be at risk while we wait years for the results of more definitive randomized controlled trials. SB 971 is important for the simple reason that people have the right to make decisions about their health based on the best available information.

Tomorrow I'll go into what I view as another reason why it's important to empower patients with this kind of information.