Does Tumor Size Predict Response to Neoadjuvant Chemotherapy in the Modern Era of Biologically Driven Treatment? A Nationwide Study of US Breast Cancer Patients

Abstract Background Tumor size has historically been used to stage breast cancer and guide treatment recommendations. The importance of tumor biology in long-term outcomes is increasingly being acknowledged. No large studies have examined the relative roles of tumor size and receptor status on response to neoadjuvant chemotherapy (NAC) in breast cancer. Patients and Methods The National Cancer Database was queried for women who underwent NAC and surgery for unilateral clinical stage I to III (cT1-3) invasive breast cancer from 2010 to 2013. Multivariable logistic regression models were used to assess the relation between receptor status, tumor size, and pathologic complete response (pCR) while controlling for other biologic, sociodemographic, diagnosis, and treatment factors. Results We included 38,864 women in this study, most presented with cT2 disease (55%). Patients predominantly had estrogen receptor (ER)/progesterone receptor (PR)-positive (ER/PR + ) HER2 − (45%) or ER/PR − HER2 − (28%) disease. Nineteen percent (7432 patients) had a pCR. cT3 (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.59-0.70) but not cT2 cancers (OR, 0.95; 95% CI, 0.89-1.02) were associated with lower pCR rates compared with cT1 disease. HER2 + (ER/PR + HER2 + : OR, 2.94; 95% CI, 2.72-3.18; ER/PR − HER2 + : OR, 6.45; 95% CI, 5.92-7.02) and ER/PR − HER2 − cancers (OR, 3.94; 95% CI, 3.68-4.22) were more likely to experience pCR than those with ER/PR + HER2 − cancers. Receptor status was more strongly associated with pCR than tumor size. Conclusion Tumor size is independently associated with pCR after NAC after controlling for receptor status, although the effect of receptor status is stronger. These data reinforce the importance of receptor status as well as tumor size, each of which might act as surrogates for tumor biology, in setting expectations for outcomes in patients who undergo NAC.