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.