Neoadjuvant therapy facilitates breast conservation



HOUSTON – For some women with breast cancer, neoadjuvant therapy can increase the likelihood of breast-conserving treatment and may limit the extent of axillary dissection, a breast cancer researcher says.

“Neoadjuvant chemotherapy has long been used in the management of inflammatory breast cancer, in patients with locally advanced, or inoperable disease, and it’s increasingly being used in patients who have operable breast cancer,” said Dr. Elizabeth A. Mittendorf of the University of Texas MD Anderson Cancer Center, Houston.

Dr. Elizabeth A. Mittendorf

Dr. Elizabeth A. Mittendorf

A meta-analysis published in 2007 suggested that neoadjuvant therapy in patients with operable breast cancer reduced the mastectomy rate by 17%, a figure that Dr. Mittendorf said likely underestimates the benefit, because many of the trials included in the analysis did not require patients to be considered for breast conservation at presentation.

The meta-analysis also showed that local recurrence rates did not differ from those seen with mastectomy when patients treated with neoadjuvant therapy were downstaged to breast-conserving therapy, and that there were no differences in local recurrence rates for neoadjuvant vs. adjuvant chemotherapy stratified by type of surgery, Dr. Mittendorf said at the annual Society of Surgical Oncology Cancer Symposium.

Key clinical trials, including the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and B-27 trials, showed that neoadjuvant chemotherapy did not have an effect on either disease-free or overall survival compared with adjuvant chemotherapy, Dr. Mittendorf noted.

Response to neoadjuvant chemotherapy is also a good predictor of prognosis, she said, pointing to a pooled analysis of 12 studies published in 2014 in The Lancet. The authors of the analysis reported that patients with a pathologic complete response (pCR; no invasive disease in either the breast or axilla) after neoadjuvant chemotherapy had significantly improved survival, with the greatest prognostic values seen in patients with aggressive tumor subtypes.

Factors to consider when selecting neoadjuvant chemotherapy include:

• Tumor size.

• Lymph node status.

• Estrogen, progesterone, and/or HER2 status.

• Treatment sensitivity (as measured by Ki-67 or other markers).

• Pathologic complete response rates.

Chemo for HR-positive?

“With respect to hormone receptor–positive breast cancer, I think the most important question for these patients is do they even need chemotherapy?” Dr. Mittendorf said.

Hormone receptor–positive (HR-positive) breast cancers have been shown to be less responsive to neoadjuvant chemotherapy, and pCR is less prognostic of outcome in this tumor subtype. Older patients with HR-positive cancers who are borderline candidates for breast-conserving therapy might benefit from neoadjuvant therapy with an aromatase inhibitor, she noted.

HER2-positive disease

For patients with HER2-positive breast cancers, it may be possible to tailor neoadjuvant therapy, so that patients who achieve a pCR with neoadjuvant trastuzumab (Herceptin) might be spared an additional 6 months of adjuvant therapy. Dr. Mittendorf’s group published a recent study

Combination anti-HER2 therapies (trastuzumab and pertuzumab [Perjeta] as used in the NeoSphere Trial may help to improve pCR rates and outcomes in patients with HER2-positive tumors, Dr. Mittendorf said.

Triple negative disease

Among patients with triple-negative breast cancer (tumors lacking hormonal receptors and HER2), those who have residual cancer after neoadjuvant chemotherapy have a poor prognosis. At MD Anderson, patients with localized triple-negative breast cancer who are scheduled to receive neoadjuvant chemotherapy first have a biopsy with molecular profiling, and are immediately started on an anthracycline-based regimen.

Patients who have a response to the chemotherapy proceed to receive a taxane, while nonresponders will be triaged onto phase II studies based on the subtype of triple-negative breast cancer. Patients who are positive for BRCA mutations will be started on a carboplatin/paclitaxel regimen, while those with mesenchymal tumor subtypes will be started on a phosphoinositide 3-kinase (PI3K) inhibitor, and those with basal-like tumors will be started on an immunotherapy protocol.Better understanding of the biology of different tumor subtypes may also help to reduce the extent of axillary surgery, by helping clinicians to identify those patients who are likely to have a nodal pCR, Dr. Mittendorf said.

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