BOSTON – The majority of patients with hormone receptor–negative breast cancer in the United States get chemotherapy in the adjuvant setting, but neoadjuvant chemotherapy is gaining in use, and is associated with a higher likelihood of breast-conserving surgery for some women with advanced disease, as well as less extensive axillary node dissection.
A review of data on more than 130,000 patients with breast tumors negative for both estrogen and progesterone receptors (ER–/PR–) showed that among patients with clinical stage T3 disease, 26% of those who had received neoadjuvant chemotherapy were able to have breast-conserving surgery, compared with 20% of patients who had received adjuvant chemotherapy, reported Dr. Carlos A. Puig and his colleagues from the Mayo Clinic in Rochester, Minn.
“Patients treated with neoadjuvant chemotherapy have less extensive axillary surgery and a lower rate of nodal positivity,” he added at the annual Society of Surgical Oncology Cancer Symposium.
The data showed that nearly a third of all patients with clinically node-positive disease (cN1-3) who received neoadjuvant chemotherapy had pathologically node-negative disease at the end of therapy.
The aggressive biology of ER–/PR– tumors makes them suitable targets for chemotherapy in the neoadjuvant setting, Dr. Puig said. Overall survival among patients with ER–/PR– who receive neoadjuvant chemotherapy is comparable to that of patients who receive chemotherapy in the adjuvant setting. Neoadjuvant regimens can also downstage tumors before surgery, and a pathologic complete response to chemotherapy delivered prior to surgery is prognostic for outcomes.
Trends in chemotherapy
Dr. Puig and his colleagues combed through the National Cancer Data Base, looking for trends in national practice patterns of use of neoadjuvant chemotherapy in ER–/PR– breast cancer from 2004 through 2012.
They identified a total of 108,128 patients with invasive ER–/PR– breast cancer who received adjuvant chemotherapy, and 24,848 who received neoadjuvant chemo; an additional 43,969 patients who did not receive chemotherapy were excluded from the analysis.
Factors significantly associated with the choice to administer neoadjuvant chemotherapy included age younger than 50, no comorbidities vs. one or two comorbidities on the Charlson/Deyo index, academic/research center vs. community cancer program, higher clinical T stage, and higher clinical N stage.
There was a gradual increase in the use of neoadjuvant chemotherapy over time, from 14.2% in 2004 to 22.3% of all patients in 2012 (P less than .001).
The overall breast-conserving surgery rates were lower among patients who had chemotherapy in the neoadjuvant setting – 33.2% vs. 54.7% (P less than .001). The rates of conservative surgery increased over time, from 32% in 2004 to 36% in 2012 (P less than .001), but decreased over the same period in patients who had adjuvant chemotherapy, from 58% to 51%, respectively.
In a breakdown of surgery type by clinical T stage, mastectomy was more frequently performed in patients who had undergone neoadjuvant treatment, compared with adjuvant therapy, except for stage T3 disease. A higher percentage of those with T3 tumors who had neoadjuvant therapy had breast-conserving surgery in comparison with women who had T3 tumors and adjuvant therapy (26.2% vs. 20.2%, respectively; P less than .001).
To identify the extent of axillary surgery, the authors considered one to five nodes removed to be a surrogate for sentinel lymph node biopsy, and six or more nodes as a surrogate for axillary lymph node dissection.
They found that among patients with clinical stage N1 through N3 who received neoadjuvant chemotherapy, 31.8% converted to pathologically node-negative status.
Dr. Puig noted that the study was limited by the retrospective design and the lack of data on HER2 receptor status, making it impossible to distinguish between ER–/PR– and triple-negative tumors. In addition, they did not have data on genetic testing that could affect surgical choices, such as the presence of BRCA1 or BRCA2.
Following Dr. Puig’s presentation, Dr. Monica Morrow, chief of breast surgery at Memorial Sloan-Kettering Cancer Center, New York, commented that the study put together “patients in whom we would consider there to be an absolute indication for neoadjuvant chemotherapy – meaning T4, N2-N3 – and patients where it’s optional.” The study results suggested that not all patients who should receive neoadjuvant therapy were getting it “which is a little disturbing,” Dr. Morrow said.
She also noted that the decrease in the use of axillary lymph node dissection began prior to publication of studies suggesting that it might be safe to do so.
Dr. Puig and Dr. Morrow had no relevant disclosures.