The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

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Metastatic breast cancer is usually diagnosed after becoming symptomatic, at which point it is rarely curable. Cell-free circulating tumor DNA (ctDNA) contains tumor-specific chromosomal rearrangements that may be interrogated in blood plasma. We evaluated serial monitoring of ctDNA for earlier detection of metastasis in a retrospective study of 20 patients diagnosed with primary breast cancer and long follow-up. Using an approach combining low-coverage whole-genome sequencing of primary tumors and quantification of tumor-specific rearrangements in plasma by droplet digital PCR, we identify for the first time that ctDNA monitoring is highly accurate for postsurgical discrimination between patients with (93%) and without (100%) eventual clinically detected recurrence. ctDNA-based detection preceded clinical detection of metastasis in 86% of patients with an average lead time of 11 months (range 0–37 months), whereas patients with long-term disease-free survival had undetectable ctDNA postoperatively. ctDNA quantity was predictive of poor survival. These findings establish the rationale for larger validation studies in early breast cancer to evaluate ctDNA as a monitoring tool for early metastasis detection, therapy modification, and to aid in avoidance of overtreatment.

Two hundred seven mucinous breast carcinomas were morphologically classified into two different groups: pure mucinous carcinomas consisting only of areas with small epithelial islands of solid tumor floating in abundant extracellular mucin, and mixed carcinomas where the tumor contains large areas of mucin, as well as areas with infiltrating carcinoma devoid of extracellular mucin. Of the 207 tumors, 95 were of the pure type and 112 of the mixed type. The pure and mixed carcinomas differed significantly with respect to a number of prognostic factors, the most important of which was lymph node status. Patients with pure mucinous carcinomas had significantly fewer lymph node metastases at the time of primary operation (P = 0.0001) and a significantly longer recurrence-free survival (P = 0.03) than patients with mixed carcinomas. Patients with mixed carcinomas closely resembled patients with infiltrating ductal carcinomas not otherwise specified (NOS) with respect to both lymph node status and recurrence-free survival. In multivariate analysis, the single most important factor for predicting recurrence-free survival among the 207 patients was lymph node status. However, of 94 pure carcinomas, only 6 had lymph node metastases at the time of mastectomy. A detailed morphologic analysis demonstrated that two of these six cases were incorrectly diagnosed as being pure mucinous carcinomas--they were actually of the mixed type. In another two of these cases, the metastases originated from a co-existent infiltrating ductal carcinoma. Thus, metastases to the regional lymph nodes were observed in only two cases of pure mucinous carcinomas. It is concluded that the biologic behavior of the pure mucinous carcinomas differs from that of both the mixed carcinomas and infiltrating ductal carcinomas NOS. Thus, a new definition is suggested, in which a mucinous carcinoma is classified as such only if it is a pure carcinoma, and mixed mucinous carcinomas are classified according to the component without extracellular mucin production.

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