Phylogenetic analysis of combined lobular and ductal carcinoma of the breast.

Breast cancer manifests in diverse forms, with particular reference to various cell types harboring different mutations and gene expression profiles. To elucidate the clonal relationship between cancer cells in tumors composed of both ductal and lobular phenotypes, two combined lobular and ductal carcinoma (CLDC) cases were analyzed, including one mixed ductal­lobular carcinoma (MDL) lesion, by direct sequencing of the mitochondrial DNA D­loop, digital PCR targeting of chromosomes 1q and 16q, as well as next­generation sequencing. DNA was extracted from formalin­fixed paraffin­embedded tissue sections of different histological types, including invasive ductal carcinoma, invasive lobular carcinoma, ductal carcinoma in situ, lobular carcinoma in situ, flat epithelial atypia, non­neoplastic mammary gland and extramammary organs, using laser­assisted microdissection. Mutations detected by the comprehensive cancer panel were validated by SYBR green allele­specific quantitative PCR (RRM1, AKT1, PIK3CA, RALGDS, EGFR, TP53, IL21R, DPYD, SGK1, CDH1, TIMP3 and KMT2C). CLDC, which shared the basic genetic alterations of 1q gain or 16q loss, progresses to invasive lobular or ductual carcinoma with the accumulation of further mutations. Cancer cells contained in an MDL lesion shared closely related genetic alterations, suggesting that these cells have the same origin, despite different histological features, namely 'lobular' or 'ductal'. By contrast, multiple lesions located away from the main tumor, diagnosed as CLDC (excluding an MDL lesion) were not always identical with different genetic alterations, despite being diagnosed as ductal carcinoma in situ. Thus, MDL should be defined as a distinct category separate from CLDC, whose components of 'lobular' and 'ductal' may have the same cellular origin.

Goserelin plus tamoxifen compared to chemotherapy followed by tamoxifen in premenopausal patients with early stage-, lymph node-negative breast cancer of luminal A subtype.

OBJECTIVES: To study the outcomes of adjuvant goserelin combined with tamoxifen (GosTam) compared to chemotherapy followed by tamoxifen (ChemTam) in premenopausal patients with early stage, luminal A breast cancer. METHODS: From 2008 until 2013, data were retrospectively collected for premenopausal patients who underwent surgery for invasive tumors that were ≤2.0 cm, node-negative, strongly positive for estrogen and progesterone receptors, HER-2-negative, and Ki-67 < 25%. The patients were divided into two groups according to adjuvant regimen, either GosTam or ChemTam. All patients who underwent different adjuvant regimens were excluded. RESULTS: In total, 235 patients underwent GosTam and 171 patients underwent ChemTam. There were significantly more patients younger than 40 years in the GosTam group (32% GosTam vs. 22% ChemTam, p = 0.031). Mean tumor size was significantly smaller (1.19 cm vs. 1.48 cm, p < 0.001), Ki-67 significantly lower (p = 0.049), and nuclear grade was low in a significant number of patients in the GosTam group (2% vs. 13%, p < 0.001). After a median follow-up of 51.3 months, there was no mortality in either group. There was no significant difference in 5-year disease-free survival (DFS) between the two groups even after univariate analysis considering age, tumor size, nuclear grade, and P53% (GosTam = 98.9% vs. ChemTam = 95.7%, HR = 0.404, 95% CI = [0.073, 2.222], p = 0.248). CONCLUSION: There was no difference between treatment groups, and neither chemotherapy nor ovarian suppression seemed to improve the outcome. Thus, tamoxifen alone might be a sufficient option for this low-risk patient population.

Association of immunohistochemically defined molecular subtypes with clinical response to presurgical chemotherapy in patients with advanced breast cancer.

Gene expression profiling (GEP) has identified several molecular subtypes of breast cancer, with different clinico-pathologic features and exhibiting different responses to chemotherapy. However, GEP is expensive and not available in the developing countries where the majority of patients present at advanced stage. The St Gallen Consensus in 2011 proposed use of a simplified, four immunohistochemical (IHC) biomarker panel (ER, PR, HER2, Ki67/Tumor Grade) for molecular classification. The present study was conducted in 75 newly diagnosed patients of breast cancer with large (>5cm) tumors to evaluate the association of IHC surrogate molecular subtype with the clinical response to presurgical chemotherapy, evaluated by the WHO criteria, 3 weeks after the third cycle of 5 flourouracil, adriamycin, cyclophosphamide (FAC regimen). The subtypes of luminal, basal-like and HER2 enriched were found to account for 36.0 % (27/75), 34.7 % (26/75) and 29.3% (22/75) of patients respectively. Ten were luminal A and 14 luminal B (8 HER2 negative and 6HER2 positive). The triple negative breast cancer (TNBC) was most sensitive to chemotherapy with 19% achieving clinical-complete-response (cCR) followed by HER2 enriched (2/22 (9%) cCR), luminal B (1/6 (7%) cCR) and luminal A (0/10 (0%) cCR). Heterogeneity was observed within each subgroup, being most marked in the TNBC although the most responding tumors, 8% developing clinical-progressive-disease. The study supports association of molecular subtypes with response to chemotherapy in patients with advanced breast cancer and the existence of further heterogeneity within subtypes.

Determining the morphological features of breast cancer and predicting the effects of neoadjuvant chemotherapy via diagnostic breast imaging.

BACKGROUND: Neoadjuvant chemotherapy has recently become common therapy for breast cancer. This work studied whether or not the effects of neoadjuvant chemotherapy can be predicted from morphological features of breast cancer in initial diagnostic imaging. MATERIALS AND METHODS: A total of 186 cases who underwent neoadjuvant chemotherapy at this hospital in 2006 were studied. Morphological features were classified into four categories. One is a type of invasive carcinoma that tends to grow along the mammary ducts (type A1), another is a type of expansively growing invasive carcinoma that is relatively well-defined (type A2), a third is a type of irregularly shaped mass that retracts surrounding tissue (type A3), and the fourth is a mixed type. Thus, the effects of neoadjuvant chemotherapy on carcinomas of the four types were compared on the basis of image and pathological findings. Effects of neoadjuvant chemotherapy were classified into three categories of enlarged mass, pCR, and other, with the latter indicating no change or shrinkage. RESULTS: Of the 186 total cases, 72 were classified as type A1, 31 as type A2, 52 as type A3, and 31 as a mixed type. Seven of 31 cases of type A2 (22.6%) were cases of an enlarged mass, revealing a high percentage of such cases. Dividing cases into type A2 and other types and looking at the proportion of cases of an enlarged mass thus indicated a significantly higher tendency. pCR was achieved in 6 of 31 cases with type A2 (19.4%). Here, also, the proportion of type A2 cases was significantly higher. CONCLUSION: Morphological features prior to neoadjuvant chemotherapy can contribute to determining the effects of the therapy. Expansively growing well-defined masses contain lesions at both extremes, tending to enlarge in some instances or instead allowing pCR, so the course of therapy must be carefully followed when performing neoadjuvant chemotherapy.