The Value of Adjuvant and Neoadjuvant Therapy for Breast Cancer

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2011 Update in Breast Cancer: Coverage of the American Society of Clinical Oncology (ASCO) Annual Meeting CME/CE Certified Course. The course is under the direction of Kevin Fox, MD, medical director of the Rena Rowan Breast Center. This is the last of four posts about the latest findings in treating breast cancer.

More News on Aromatase Inhibitors (AIs)
A group of bone health-related studies (Abstracts 516, 517, 518) presented at the 2011 ASCO conference provided some good news on bone loss. The studies showed that postmenopausal breast cancer patients undergoing endocrine therapy (aromatase inhibitors) do not experience an increase in their total number of fractures, despite having some level of bone loss.

Over a period of approximately six years, 5 percent of patients receiving aromatase inhibitors (AIs) suffered fragility fractures, the same percentage as occurred in the control group. Studies also show that exemestane may result in less bone loss than other AIs.

A third set of AI studies (Abstracts 522,523 525) strengthened the data supporting the proposition that women who experience endocrine-related symptoms, specifically arthralgia and bone pain, while taking AIs do have improved treatment efficacy.

Regional vs. Whole Breast Irradiation for Node-Positive Cancer
The controversy regarding the optimal treatment approach for breast cancer with one to three positive nodes has existed for some time. Current treatment guidelines call for regional lymph node irradiation (RNI) for all patients with four or more positive nodes, but have been less clear about the role of RNI in cases involving one to three nodes.

Another trial highlighted at the ACO conference, NCIC-CTG MA.20, bolsters the view that all node-positive breast cancer patients should be considered for RNI.

In this large, intergroup trial, women with positive nodes or high-risk node negative breast cancer were treated with breast-conserving surgery. They were then randomized to receive either standard whole breast irradiation (WBI) or WBI plus RNI. The study demonstrated a clear advantage for the WBI plus RNI group for five year overall and disease-free survival. They did experience modestly increased toxicity, mostly attributable to a slight increase in grade II lymphedema.

Focus on Neoadjuvant Therapy for HER2-Positive Breast Cancer
Neoadjuvant therapy, or therapy that is given before primary cancer treatment, is becoming a standard way to study new approaches to treating breast cancer. Angela DiMichele, MD, assistant professor of medicine and epidemiology at the Perelman School of Medicine at the University of Pennsylvania, noted the emphasis on neoadjuvant therapy at the ASCO meeting, citing several studies for women with HER2-positive breast cancer, a group for which there is a growing number of treatment options.

The first (abstracts 505, 507) combined lapatinib and trastuzamab in a neoadjuvant setting without chemotherapy for women with HER2-postive tumors >3cms or >2cms with palpable nodes. The results were positive with an overall pCR of 28 percent and a 40 percent pCR in ER- negative patients and strengthened the evidence for the dual receptor blockade as the new standard of therapy for HER2-positive tumors. The study did have an 8 percent drop out rate resulting from toxicity, primarily diarrhea and acne form rash.

The other studies (abstracts 531, 532) looked at the results of adding chemotherapy to the dual receptor blockade. The first demonstrated a clear advantage to lapatinib and trastuzamab with anthracycline-taxane therapy in terms of pCR, but left unanswered issues as to whether the increased toxicity with chemotherapy is worth the risk and whether the pCR will translate into long-term survival.

Triple-Negative Breast Cancer
While the options for HER2-postive patients continue to expand and improve, the need remains to discover more effective therapies for the 15 percent of patients diagnosed with triple negative breast cancer (TNBC). While considerable attention was focused on TNBC at ASCO 2011, the meeting did not yield significant progress for women with this disease.

Several trials offered data suggesting that basal subtypes of breast cancer might be sensitive to platinum, but much more information is needed to clarify which subgroups of patients and under which circumstances will benefit from this therapy (Abstract 1015). Similar issues apply to the use of agents targeted to the mTOR and PI3K pathways (abstract 1016). The conclusion: For TNBC, a commitment to larger, well-designed trials with integrated, adequately-powered biomarker assessment are needed.

Abstracts can be found on the 2011 ASCO meeting website.

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