Axillary pCR Predicts Breast Cancer Survival after Primary Systemic Chemotherapy

Axillary pathological complete response is a positive prognostic indicator for breast cancer patients given neoadjuvant chemotherapy

medwireNews: Residual disease in the axilla significantly reduces long-term overall survival (OS) and relapse-free survival (RFS) in breast cancer patients who are treated with primary systemic chemotherapy (PST), US researchers have found.

Vicente Valero, from the University of Texas MD Anderson Cancer Center in Houston, and co-authors, report in JAMA Oncology the 10-year outcomes of 1600 patients diagnosed with stage II–III tumours and cytologically confirmed axillary metastases between 1989 and 2007.

Overall, 28.4% of patients achieved a pathological complete response (pCR) in the axilla, and this outcome was significantly predicted by human epidermal growth factor receptor (HER2)-positive and triple-negative disease, a pCR in the breast, high-grade tumour and lower T stage.

The 10-year OS and RFS rates were significantly higher for women who achieved axillary pCR compared with those who had residual disease, at 84% versus 57%, and 79% versus 50%, respectively.

And the 10-year OS rate for women with axillary pCR but residual breast disease was 72% compared with 66% for women with breast pCR but residual axillary disease, suggesting that  “clearance of axillary metastases is more important than clearance of disease in the breast”, say Vicente Valero et al.

“This finding may relate to the inherent biological characteristics and increased metastatic potential of axillary metastases”, they hypothesise, adding that further research is required “to determine whether patients with residual disease after PST, particularly in the axillary lymph nodes, may benefit from further therapy after surgery to reduce the risk of relapse and improve survival.”

Of note, the best rates of pCR were found among the 149 patients with a known HER2-positive status who received targeted therapy; an axillary pCR was achieved by 67.1% of these women compared with 32.6% of 187 who did not receive trastuzumab or other targeted agents. Ten-year OS rates were 92.0% versus 57.0% for HER2-positive patients with and without an axillary pCR.

In an accompanying comment, Monica Morrow, from Memorial Sloan Kettering Cancer Center in New York, USA, describes the low rates of pCR in all but the HER2-positive patients as “disappointing” and questions whether PST is, as the authors state, the “standard of care” for patients with large operable and locally advanced disease.

She writes that while the rationale for neoadjuvant chemotherapy is to make breast-conserving surgery feasible in women with large tumours, patient preference for mastectomy means it may not significantly reduce rates of the procedure.

Additionally, while axillary pCR may be used to reduce the need for axillary dissection, the commentator observes that sentinel node biopsy is only accurate in the minority of women who have axillary pCR and have staging of three or more sentinel nodes.

The study “provides further information that helps to tailor our approach to neoadjuvant therapy in operable breast cancer outside clinical trials”, writes Monica Morrow.

“Patients with clinically node-positive (palpable) disease at presentation, those with larger tumors desiring breast conservation, and those with HER2-overexpressing tumors have a clear rationale for neoadjuvant therapy.

“For the remainder, it is an option, but it cannot be considered the standard of care.”

References

Mougalian SS, Hernandez M, Lei X, et al. Ten-year outcomes of patients with breast cancer with cytologically confirmed axillary lymph node metastases and pathologic complete response after primary systemic chemotherapy. JAMA Oncol; Advance online publication 30 December 2015. doi:10.1001/jamaoncol.2015.4935

Morrow M. Parsing pathologic complete response in patients receiving neoadjuvant chemotherapy for breast cancer. JAMA Oncol; Advance online publication 30 December 2015. doi:10.1001/jamaoncol.2015.4919

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