In women with early breast cancer, neoadjuvant chemotherapy (NACT) results in higher rates of breast-conserving therapy than adjuvant chemotherapy, without compromising on distant recurrence, breast cancer survival, or overall survival, but with higher rates of local recurrence, new research indicates.
“Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumors downsized by NACT should be considered – for example, careful tumor localization, detailed pathological assessment, and appropriate radiotherapy,” the researchers advise in an article online December 11 in Lancet Oncology.
The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) did a meta-analysis of individual patient data from 10 trials that compared NACT with the same chemotherapy given postoperatively in 4,756 women with early breast cancer. The women entered the trials between 1983 and 2002, and median follow-up lasted 9 years. Most chemotherapy was anthracycline-based.
According to the research team, more than two thirds (69%) of women who received NACT had a complete or partial clinical response. Response was more common in women with hormone receptor-negative or high-grade tumors but was little affected by age, nodal status, or planned local therapy.
As expected, NACT was associated with an increase in use of breast-conserving therapy (65% with NACT vs. 49% with adjuvant chemotherapy), but also with a moderately increased local recurrence risk (21.4% vs. 15.9%; rate ratio, 1.37; P=0.0001).
NACT and adjuvant chemotherapy showed no marked differences in distant recurrence, breast cancer mortality, or death from any cause.
“The main aim of NACT in contemporary practice is to reduce the extent of breast surgery, thereby making breast conservation feasible in women who would otherwise need mastectomy,” the researchers point out. “In the time since the trials in this meta-analysis were done, pathology reporting, surgery, and radiotherapy have improved, and more effective systemic neoadjuvant regimens have been introduced than were available when these trials took place. These changes should increase the likelihood of successful downstaging to allow conservative surgery in current and future practice,” they note.
They add, “although improvements in treatment mean local recurrence risk should be lower than in these trials, our findings indicate that tumors downsized by NACT might continue to be associated with higher local recurrence risk after breast-conserving surgery than might tumors of the same dimensions in women who have not received NACT.”
The authors of a linked Comment say, “Whether NACT itself could be held accountable for the small increase in local recurrences is questionable. Higher local recurrence with breast-conserving surgery than with mastectomy is inherent to breast-conserving therapy.”
“With the evidence generated from this meta-analysis, patients with large tumors can be recommended to have NACT and subsequent breast-conserving surgery depending on response assessment. Further studies will tailor the optimum extent of breast and axillary treatment on the basis of response to NACT,” write Dr. Marloes Derks and Dr. Cornelis van de Velde from Leiden University Medical Center, the Netherlands.
The study had no commercial funding, and the authors have disclosed no conflicts of interest.
SOURCES: http://bit.ly/2BIFUTx and http://bit.ly/2CQQ7g0
Lancet Oncol 2017.
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