Wednesday, December 14, 2011

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 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, everyday. The latest news and research may be explored anytime by clicking the Treatments tab.

Tuesday, December 13, 2011

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 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, 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.

Tuesday, December 6, 2011

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 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.