Neoadjuvant chemotherapy tied to increased local recurrence risk after breast conservation
While neoadjuvant chemotherapy is comparable to adjuvant chemotherapy in reducing the risk of distant recurrence and mortality in women with early breast cancer, it is associated with a higher risk of local recurrence, according to a meta-analysis conducted by the EBCTCG*.
“[Neoadjuvant chemotherapy] allows more breast-conserving therapy than does adjuvant chemotherapy and provides information about an individual patient’s response to a particular chemotherapy regimen. [However], tumours downsized by [neoadjuvant chemotherapy] might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received [neoadjuvant chemotherapy],” said the researchers.
Researchers used individual patient data of 4,756 women (median age 49 years) with early, operable breast cancer enrolled in 10 randomized trials between 1983 and 2002 who were followed-up for a median 9 years.
Most women (81 percent) underwent anthracycline-based regimens. Sixty-nine percent of women given neoadjuvant chemotherapy had either a complete or partial clinical response (28 and 41 percent, respectively), with 83 and 68 percent, respectively undergoing subsequent breast conservation treatment. Women given neoadjuvant chemotherapy were more likely to undergo breast-conserving therapy compared with those given adjuvant chemotherapy (65 percent vs 49 percent).
Small tumour size, oestrogen receptor- and progesterone receptor-negative, and high-grade tumours prior to randomization were factors associated with response, while age, nodal status, and planned local therapy had little effect.
At 15 years, the local recurrence rate was significantly higher among women who underwent neoadjuvant compared with adjuvant chemotherapy (21.4 percent vs 15.9 percent, rate ratio [RR], 1.37, 95 percent confidence interval [CI], 1.17–1.61; p=0.0001). [Lancet Oncol 2018;19:27-39]
Conversely, the distant recurrence rate at 15 years was comparable between patients given neoadjuvant and adjuvant chemotherapy (38.2 percent vs 38.0 percent, RR, 1.02, 95 percent CI, 0.92–1.14; p=0.66).
The rates of breast cancer mortality and any-cause mortality were also similar between patients given neoadjuvant and adjuvant chemotherapy (34.4 percent vs 33.7 percent, RR, 1.06; p=0.31 and 40.9 percent vs 41.2 percent, RR, 1.04; p=0.45, respectively).
“An increase in the use of breast-conserving therapy in women who responded well to [neoadjuvant chemotherapy] and who would otherwise have had mastectomy is a likely explanation for the increase in local recurrence [among these patients],” said the researchers, citing that the highest absolute increase in local recurrence occurred in the two trials in which some women who had a complete response to neoadjuvant chemotherapy did not undergo subsequent surgery. However, the nonsignificant heterogeneity between these two and the other eight trials suggests that the incidence of local recurrence may not be completely due to lack of surgery, they said.
“Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by [neoadjuvant chemotherapy] should be considered—for example, careful tumour localization, detailed pathological assessment, and appropriate radiotherapy,” said the researchers.