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Background: The mechanism of late recurrence (LR) of estrogen receptor (ER)-positive breast cancer remains unclear, as previous studies have separately investigated "gene expression profiles" and "clinicopathological factors." Thus, this study aimed to evaluate the predictive capability of LR by combining the two independent factors of gene expression profiles (42-gene classifier: 42GC) and clinicopathological factors (Clinical Treatment Score post-5 years: CTS5) in multiple large cohorts. Methods: We analyzed microarray CEL file data downloaded from public databases of 28 global cohorts. A total of 2,454 patients with ER-positive breast cancer were analyzed for 42GC, and 1,263 of these, with complete clinicopathological data were analyzed for CTS5. Results: In the analysis of recurrent patients, the 42GC LR and CTS5 low-risk group tended to have LR. Notably, in the analysis of patients with and without recurrence, the highest LR rate beyond 5 years was observed in the CTS5 high-risk group. The combination of the 42GC and CTS5 high-risk groups showed the highest LR rate (16.9%), significantly exceeding that of the 42GC non-LR (NLR) and CTS5 low-risk combination (5.41%) (p = 0.038, odds ratio = 3.53). Furthermore, incorporating a third factor, 95GC, potentially reduced the number of patients prioritized for extended hormonal therapy for approximately one-quarter of patients. Conclusions: Results confirmed that the two factors, gene expression profiles and clinicopathological factors, affect the time of recurrence. It also showed that the biological predisposition for LR (CTS5 low-risk) differed from the high LR rate (CTS5 high-risk). In clinical practice, patients with the 42GC LR and CTS5 high-risk combination should be prioritized for extended hormonal therapy. The addition of CTS5 and 95GC to 42GC allows for better risk classification of LR. [ABSTRACT FROM AUTHOR]

Background: EndoPredict® (EP) is a multigene assay to predict distant recurrence risk in luminal breast cancer. EP measures the expression of 12 genes in primary tumor by qRT-PCR from formalin-fixed paraffin-embedded (FFPE) tissues and calculates EP risk score that indicates the risk of distant recurrence. We evaluated the performance of EP in predicting distant recurrence risk using microarray data from fresh frozen (FF) tissues. We also examined the applicability of EP to microarray data from FFPE tissues. Methods: We analyzed the publicly available data of 431 node-negative and 270 node-positive patients with luminal breast cancer who received endocrine therapy alone. We evaluated the prognostic value of EP using microarray data from FF tissues. Next, we created an algorithm to calculate EP risk score using microarray data from FFPE tissues. We examined the correlation coefficient of EP risk score and concordance rate of EP risk high/low using microarray data from FFPE/FF tissue pairs in a validation set of 39 patients. Results: In 431 node-negative patients, the distant recurrence-free survival (DRFS) rate was significantly worse in those with high EP risk scores (P = 3.68 × 10−6, log-rank). The 5-year DRFS was 95.2% in those with low EP risk score. In the validation set, the correlation coefficient of EP risk score was 0.93 and the concordance rate of EP risk high/low was 91.7%. Conclusions: EP using microarray data from FF tissues was useful in predicting distant recurrence risk in luminal breast cancer, and EP might be utilized in microarray data from FFPE tissues. [ABSTRACT FROM AUTHOR]

Background: Due to the lack of clinical trials on the efficacy of chemotherapy in older patients, an optimal treatment strategy has not been developed. We investigated whether adjuvant chemotherapy could improve the survival of older patients with breast cancer in Japan. Methods: We retrospectively analyzed data of patients with breast cancer aged ≥ 70 years who underwent breast cancer surgery in eight hospitals between 2008 and 2013. Clinical treatment and follow-up data were obtained from the patients' medical electric records. Results: A total of 1095 patients were enrolled, of which 905 were included in the initial non-matched analysis. The median age and follow-up period were 75 (range 70–93) and 6.3 years, respectively. Of these patients, 127 (14%) received adjuvant chemotherapy (Chemo group) while the remaining 778 (86%) did not (Control group). The Chemo group was younger (mean age in years 73 vs 76; P < 0.0001), had a larger pathological tumor size (mean mm 25.9 vs 19.9; P < 0.0001), and more metastatic axillary lymph nodes (mean numbers 2.7 vs 0.7; P < 0.0001) than the Control group. The disease-free survival (DFS) and overall survival (OS) did not differ significantly between the two groups (P = 0.783 and P = 0.558). After matched analyses, DFS was found to be significantly prolonged with adjuvant chemotherapy (P = 0.037); however, OS difference in the matched cohort was not statistically significant (P = 0.333). Conclusion: The results showed that adjuvant chemotherapy was associated with a reduced risk of recurrence, but survival benefits were limited. [ABSTRACT FROM AUTHOR]

Background: The standard primary systemic therapy for human epidermal growth factor receptor 2-positive (HER2+) breast cancer is anthracyclines and/or taxanes combined with trastuzumab, which demonstrates a high pathological complete response (pCR). A pCR is a predictive marker of prognosis. However, results slightly differ, depending on the hormone receptor status. The efficacy and tolerability of docetaxel, cyclophosphamide, and trastuzumab (HER-TC) as neoadjuvant chemotherapy (NAC) remain unclear. We performed a prospective multicenter study of HER-TC NAC for HER2+ primary breast cancer. Methods: Eligible patients had a clinical diagnosis of HER2+ invasive breast cancer greater than 1 cm but less than 7 cm and a tumor stage of N0 or N1. T hey were diagnosed between July 2011 and February 2014. For NAC, four cycles of HER-TC (6 mg/kg loading dose, 8 mg/kg, 75, and 600 mg/m) were administered intravenously every 3 weeks. We investigated the pCR of the primary breast tumors. A pCR was defined as no histological evidence of invasive carcinoma or the appearance of only ductal carcinoma in situ. Results: We enrolled 42 patients. The completion rate for four cycles of HER-TC was 97.6 % (41/42 patients). The overall pCR rate was 43.9 % (18/41 patients). The pCR rate for patients with the luminal HER2 subtype [estrogen receptor (ER)-positive+, HER2+] and the HER2-enriched subtype (ER−, HER2+) was 40.0 % (8/20 patients) and 47.6 % (10/21 patients), respectively. A pCR was achieved with nearly the same probability for each subtype. Conclusions: Four cycles of HER-TC may be a NAC option for HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background: Docetaxel plus cyclophosphamide (TC) has recently been established as a standard adjuvant chemotherapy regimen for HER2-negative (HER2−) operable breast cancer. However, the efficacy and tolerability of TC as neoadjuvant chemotherapy (NAC) remain unclear. We, therefore, conducted a prospective study to evaluate the efficacy of TC NAC in HER2− primary breast cancer. Methods: Patients who were diagnosed with HER2−, N0-N1, invasive breast cancer between July 2011 and February 2014 and had tumors measuring 1-7 cm were eligible. The subtypes were classified using a core-needle or vacuum-assisted breast biopsy. The efficacy and safety of NAC comprising TC (75 mg/m docetaxel and 600 mg/m cyclophosphamide, four cycles every 3 weeks) were investigated in a prospective study in patients with HER2− breast cancer. Results: Fifty-two patients were enrolled. Of these, 94.2 % (49/52) completed four cycles of TC. The overall pCR rate was 16.3 % (8/49). The pCR rates for patients with luminal A-like breast cancer [estrogen receptor-positive (ER+), Ki67 index of <20 %, and HER2−], luminal B-like breast cancer (ER+, Ki67 index of >20 %, and HER2−), and triple-negative breast cancer [ER-negative (ER−) and HER2−] were 0 % (0/12), 4.3 % (1/23), and 50.0 % (7/14), respectively. Almost all pCRs occurred in triple-negative breast cancer patients. Conclusions: The pCR rate of TC NAC was not very high despite the high completion rate. TC NAC was effective against the triple-negative subtype, resulting in a higher pCR rate. Therefore, our results indicated that TC NAC showed limited efficacy in luminal subtype breast cancer with the exception of the triple-negative subtype. [ABSTRACT FROM AUTHOR]