Taxanes in Adjuvant Treatment
Many of us (including me) who have been treated in the past five or so years have received one of the Taxanes (Taxol or Taxotere) as part of our adjuvant chemotherapy. A study reported last week at ASCO's Breast Symposium may be the beginning of a change in practice. It indicated that the inclusion of these drugs only adds a benefit for a subgroup of women with breast cancer, specifically those whose tumors are of three molecular types: luminal (ER +, Her2 -, fast-growing), core basal (triple negative), and Her 2 positive. If this study does indeed begin to change standard practice, it will be far from the first time that breast cancer adjuvant therapy has changed. It can be upsetting to learn that, if your cancer were diagnosed and treated today, it likely would be a different course than you received. Treatment is forever evolving and improving, and the best any of us can get is whatever is thought to be best at our particular moment.
Here is the report:
ASCO Breast: Analysis Revises Taxane Benefit in Breast Cancer
What breastcancer.org says about this article…
ASCO Breast: Analysis Revises Taxane Benefit in Breast Cancer
After surgery for early-stage breast cancer, chemotherapy often is given to destroy any breast cancer cells that may remain in the body and reduce the risk of the cancer coming back (recurrence). Doctors call this type of treatment adjuvant chemotherapy. A number of chemotherapy medicines, given alone or in combination, are used as adjuvant chemotherapy, including a class of medicines called taxanes. Taxol (chemical name: paclitaxel), Taxotere (chemical name: docetaxel), and Abraxane (chemical name: albuminbound paclitaxel) are all taxanes.
This study found that taxanes reduce the risk of recurrence of only certain molecular types of breast cancer. So using a taxane to treat the other types of breast cancer doesn't offer any real benefits. The results were reported at the 2009 ASCO Breast Cancer Symposium. The researchers looked at more than 2,000 early-stage breast cancer tumor specimens using advanced molecular biology technology. Each specimen was put into one of five categories:
Luminal A tumors are hormone-receptor-positive, HER2-negative, and slow-growing. They were the most common type of tumor (42%).
Core basal tumors are hormone-receptor-negative, HER2-negative, and positive for other genetic
abnormalities (Ki67, CK5/6 and EGFR). They were the second most common type of tumor (24%).
Luminal B tumors are hormone-receptor-positive, HER2-negative, and fast-growing. They were the third most common type of tumor (18%).
HER2-positive cancers were the fourth most common type of tumor (12%).
Aggressive non-basal tumors are hormone-receptor-negative, HER2-negative, and negative for other genetic abnormalities. They were the least common type of tumor (5%).
The researchers reviewed the medical records of the women from whom the specimens were obtained to see if including a taxane in adjuvant chemotherapy reduced the risk of breast cancer recurrence. Taxanes didn't provide any benefits to women diagnosed with the most common (luminal A) and least common (aggressive non-basal) types of breast cancer. These two types made up 47% of the breast cancers evaluated in the study.
Taxanes offered some benefit to women diagnosed with the other three types of breast cancer (luminal B, core basal, and HER2-positive -- these three types made up 53% of the breast cancers evaluated in the study.) For example, women diagnosed with core basal breast cancer had a 25% lower risk of recurrence when they received a taxane. These results, along with similar findings from other studies, suggest that a cancer's tumor type should help guide decisions about using taxanes. While some of the tests used in this study aren't routinely done, the information that's typically in a pathology report may be enough to identify the cancer type and help you and your doctor make taxane decisions. Women who are unlikely to benefit from a taxane can avoid the possible side effects, which include nerve pain and other sensory problems (neuropathy).
If chemotherapy will be part of your treatment plan, talk to your doctor about the results of this study. Ask if the cancer's type can be identified using the information in your pathology report and if that cancer type is likely to respond to a taxane. If the information needed to determine cancer type isn't available, ask if you can get that information before any chemotherapy decisions are made. Using all the information available about your specific situation and the best available medical evidence, you and your doctor can make the best choices for you.
Research News on Chemotherapy
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SAN FRANCISCO (MedPage Today) -- Women with the most common molecular subtype of breast cancer don't benefit from the addition of paclitaxel to chemotherapy, researchers here reported, but women with the more aggressive basal subtype did see benefits.
Patients with the basal subtype saw a 25% reduction in relapse with paclitaxel (HR 0.75, P=0.033) over a long-term follow-up in the analysis of the Cancer and Leukemia Group B (CALGB) 9344 trial, investigators told attendees at the ASCO Breast Cancer Symposium. The drug did not benefit women with the more common estrogen receptor-positive, usually low-grade and slow-growing Luminal A subtype.
"If you are ER [estrogen receptor]-positive but do not have the other molecular risk factors of HER2 expression or high proliferation rate, you probably don't need paclitaxel added to your chemotherapy," said presenter Torsten O. Nielsen, MD, PhD, of the University of British Columbia in Vancouver. His group used a high-throughput tissue microarray to determine molecular tumor characteristics -- a technique that is not practical at the individual patient level.
But community practices already routinely get the basic information behind the subtypes with standard ER and HER2 assays, commented Deanna J. Attai, MD, of the Center for Breast Care and Providence St. Joseph's Medical Center in Burbank, Calif.
Lori Pierce, MD, of the University of Michigan in Ann Arbor, called these findings important for clinical practice. "The methods used will help clinicians select those breast cancers that will respond to specific chemotherapies and spare patients who can't or will not respond," said Pierce, who moderated a press briefing highlighting these results and served as co-chair of the conference program committee.
Earlier reports from the CALGB trial had established taxane-inclusive chemotherapy regimens in routine practice for women at high risk of relapse, but suggested that HER2-negative, ER-positive breast cancer did not benefit.
So, for a more detailed look at which patients benefit, Nielsen's group revisited the trial's tissue bank with technology not available when the the original work was conducted. They analyzed specimens from 2,039 of the 3,121 trial subjects, whose outcomes were representative of the trial as a whole, using tissue microarrays and an immunohistochemistry panel for ER, HER2, Ki67, cytokeratin 5/6 and epidermal growth factor receptor.
The most common subtype found was Luminal A, in 790 women. The similarly ER-positive, but fastergrowing >Luminal B subtype was also common, accounting for 340 of the breast cancer cases. The HER2-enriched subtype accounted for 221, core basal for 444, and the aggressive ER-/HER2-/nonbasal subtype for 93. These "intrinsic" subtypes significantly predicted prognosis in multivariate analysis (P<0.001). Along with the basal type that benefited from addition of paclitaxel in the trial, the 20% with HER2-positive cancers also appeared to see a relapse-free survival advantage, Nielsen said.
However, both the large number of Luminal A cancers and small group with ER-/HER2-/nonbasal tumors failed to get a significant benefit from addition of the taxane to the chemotherapy regimen. Although these results were from a retrospective, unplanned analysis, Attai said the size and quality of the study were convincing and would likely have an immediate impact on treatment recommendations.
"We're moving away from the one-size-fits-all approach to chemotherapy," she said. "This is another step toward more targeted chemotherapy." The study was funded by The Hope Foundation, the Breast Cancer Research Foundation, and a grant from the National Institutes of Health. Nielsen reported having recieved research funding from sanofi-aventis. Coauthors reported conflicts of interest with University Genomics and Monogram Biosciences.
Attai reported being an uncompensated consultant for Cianna Medical. Pierce reported having received research funding from the National Institutes of Health and the Breast Cancer Research Foundation.
Primary source: ASCO Breast Cancer Symposium Source reference: Nielsen TO, et al "Intrinsic subtype and response to paclitaxel in CALGB 9344 tissue microarrays" ASCO Breast 2009.