BackgroundEribulin is a non-taxane, microtubule dynamics inhibitor that increases survival of patients with metastatic breast cancer. Although eribulin is well tolerated in patients with heavily pretreated disease, eribulin-induced liver dysfunction (EILD) can occur, resulting in treatment modification and subsequent poor disease control. We aimed to clarify the effect of EILD on patient survival.MethodsThe medical records of 157 metastatic breast cancer patients treated with eribulin between July 2011 and November 2013 at Cancer Institute Hospital were retrospectively analyzed. EILD was defined as 1) an increase in alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal, and/or 2) initiation of a liver-supporting oral drug therapy such as ursodeoxycholic acid or glycyron. Fatty liver was defined as a decrease in the liver-to-spleen attenuation ratio to <0.9 on a computed tomography scan.ResultsEILD occurred in 42 patients, including one patient for whom eribulin treatment was discontinued due to severe EILD. The patients who developed EILD had significantly higher body mass indices (BMIs) than those who did not develop EILD (24.5 vs. 21.5, respectively; P < 0.0001), with no difference in the dose intensity of eribulin between the two groups (P = 0.76). Interestingly, the patients with EILD exhibited significantly longer progression-free survival (PFS) and overall survival (OS) than those without EILD (P = 0.010 and P = 0.032, respectively). Similarly, among 80 patients without liver metastasis, 19 with EILD exhibited significantly longer PFS and OS than the others (P = 0.0012 and P = 0.044, respectively), and EILD was an independent prognostic factor of PFS (P = 0.0079) in multivariate analysis. During eribulin treatment, 18 patients developed fatty liver, 11 of whom developed EILD, with a median BMI of 26.7.ConclusionsAlthough EILD and fatty liver occurred at a relatively high frequency in our study, most of the patients did not experience severe adverse effects. Surprisingly, the development of EILD was positively associated with patient survival, especially in patients without liver metastases. EILD may be a clinically useful predictive biomarker of survival, but further studies are needed to confirm these findings in another cohort of patients.

Background Internal mammary and/or supraclavicular (IM–SC) lymph node (LN) recurrence without distant metastasis (DM) in patients with breast cancer is rare, and there have been few reports on its clinical outcomes. Methods We enrolled 4237 patients with clinical stage I–IIIC breast cancer treated between January 2007 and December 2012. Clinicopathological features of patients with IM–SC LN recurrence and patients with DM were retrospectively reviewed. Results With a median follow-up time 78 (range, 13–125) months after the primary operation, 14 (0.3%) had IM–SC LN recurrence without DM and 274 (6.5%) had DM at the first recurrence among 4237 patients. No statistical differences were found in the baseline characteristics of the primary tumor between the two groups. The 5-year overall survival (OS) rate after recurrence in patients with IM–SC LN recurrence was 51% compared with 27% in patients with DM (P = 0.040). In patients with IM–SC LN recurrence, clinically positive axillary LN at diagnosis and pathologically positive axillary LN at primary surgery were poor prognostic factors for distant disease-free survival (DDFS) (P = 0.004 and 0.007, respectively). Clinical and pathological axillary nodal status at primary surgery was associated with OS (P = 0.011 and 0.001, respectively). Conclusions Patients with IM–SC LN recurrence without DM who had no clinical and pathological axillary LNs involved at primary surgery had a favorable prognosis. A larger validation study is required.

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Background: It is unknown whether patients with cytologically proven axillary node-positive breast cancer who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. Methods: We retrospectively reviewed the data of patients with cytologically proven axillary node-positive disease who received NAC and those with axillary pN- without NAC for control between January 2007 and December 2012. We compared outcomes according to response in the axilla to NAC and between patients with axillary pCR and matched pairs with axillary pN- without NAC using propensity scores. Results: We included 596 patients with node-positive breast cancer who received NAC. The median follow-up period was 64 months. Patients with axillary pCR showed significantly better distant disease-free survival (DDFS) and overall survival (OS) than patients with residual axillary disease (both p < 0.01). There was no significant difference in DDFS and OS between patients with axillary pCR and matched pairs with axillary pN- without NAC. Conclusion: Axillary pCR was associated with improved prognosis. Patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes. This information will be useful when considering the intensity of follow-up and adjuvant therapy.

Background ER+HER2+ breast cancer requires most types of systemic therapies perioperatively. However, treatment resistance is often experienced. The current study investigated the predictive and prognostic value of intratumoral heterogeneity and conventional clinicopathological factors in patients with ER+HER2+ breast cancer. Methods This research included two patient cohorts with ER+HER2+ breast cancer. Cohort A included patients who underwent surgery without neoadjuvant chemotherapy (NAC). Cohort B comprised patients who received NAC followed by surgery. Intratumoral heterogeneity was assessed via ER and HER2 double staining, and the number of cells stained with different patterns of ER and HER2 was counted. Results In total, 11 of 92 tumors in cohort A and four of 45 tumors in cohort B consisted exclusively of double‐positive (ER+ and HER2+) cells (homogeneous). The rest had different combinations of cells (heterogeneous). The pathological complete response (pCR) rates differed based on tumoral cell components but not intratumoral heterogeneity. The pCR rate of tumors with ER−HER2+ cells but without HER2− cells was higher than that of others (45.5% vs 4.3%; p = 0.0013). Low ER and PgR Allred scores indicated better pCR rates than high scores (p = 0.0005 and 0.024, respectively). Multivariate analysis showed that the ER Allred score and cell component of ER−HER2+ cells without HER2− cells were independent predictors of pCR (p = 0.0055 and 0.0081, respectively). In cohort B, posttreatment Ki67, but not pCR, was a prognostic factor of DFS and OS (p = 0.028 and 0.017, respectively). The prognostic value of combined posttreatment Ki67 and pCR was superior to that of either alone. Combined pCR and posttreatment Ki67 had an independent prognostic value for DFS and OS (p = 0.0068 and 0.0101, respectively). Conclusions In ER+HER2+ breast cancer, the presence of ER−HER2+ cells without HER2− cells was independently associated with pCR. Combined posttreatment Ki67 and pCR can be more precise in predicting prognosis than pCR alone.