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PURPOSE Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to overcome many of the shortcomings associated with the traditional ligand-binding assay (LBA). The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome—especially response to adjuvant endocrine therapy—in a large number of patients with long-term clinical follow-up. PATIENTS AND METHODS ER status was evaluated in 1,982 primary breast cancers by IHC on formalin-fixed paraffin-embedded tissue sections, using antibody 6F11 and standard methodology. Slides were scored on a scale representing the estimated proportion and intensity of positive-staining tumor cells (range, 0 to 8). Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. RESULTS An IHC score of greater than 2 (corresponding to as few as 1% to 10% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free survival (DFS) in patients receiving any adjuvant endocrine therapy. Using this definition, 71% of all tumors were determined to be ER-positive by IHC, and the level of agreement with the LBA was 86%. In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DFS (hazard ratios/ P = 0.474/.0008 and 0.707/.3214, respectively) and equivalent at predicting overall survival (0.379/.0001 and 0.381/.0003, respectively). CONCLUSION IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy.

Background Human epidermal growth factor receptor2+ subtype breast cancer has a high degree of malignancy and a poor prognosis. The aim of this study is to develop a prediction model for the human epidermal growth factor receptor2+ subtype (non-luminal) of breast cancer based on the clinical and ultrasound features related with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor2. Methods We collected clinical data and reviewed preoperative ultrasound images of enrolled breast cancers from September 2017 to August 2020. We divided the data into in three groups as follows. Group I: estrogen receptor ± , Group II: progesterone receptor ± and Group III: human epidermal growth factor receptor2 ± . Univariate and multivariate logistic regression analyses were used to analyze the clinical and ultrasound features related with biomarkers among these groups. A model to predict human epidermal growth factor receptor2+ subtype was then developed based on the results of multivariate regression analyses, and the efficacy was evaluated using the area under receiver operating characteristic curve, accuracy, sensitivity, specificity. Results The human epidermal growth factor receptor2+ subtype accounted for 138 cases (11.8%) in the training set and 51 cases (10.1%) in the test set. In the multivariate regression analysis, age ≤ 50 years was an independent predictor of progesterone receptor + (p = 0.007), and posterior enhancement was a negative predictor of progesterone receptor + (p = 0.013) in Group II; palpable axillary lymph node, round, irregular shape and calcifications were independent predictors of the positivity for human epidermal growth factor receptor-2 in Group III (p = 0.001, p = 0.007, p = 0.010, p Conclusions Our study established a model to predict the human epidermal growth factor receptor2-positive subtype with moderate performance. And the results demonstrated that clinical and ultrasound features were significantly associated with biomarkers.

Histopathologic evaluation of biopsy slides is a critical step in diagnosing and subtyping breast cancers. However, the connections between histology and multi-omics status have never been systematically explored or interpreted. We developed weakly supervised deep learning models over hematoxylin-and-eosin-stained slides to examine the relations between visual morphological signal, clinical subtyping, gene expression, and mutation status in breast cancer. We first designed fully automated models for tumor detection and pathology subtype classification, with the results validated in independent cohorts (area under the receiver operating characteristic curve ≥ 0.950). Using only visual information, our models achieved strong predictive performance in estrogen/progesterone/HER2 receptor status, PAM50 status, and TP53 mutation status. We demonstrated that these models learned lymphocyte-specific morphological signals to identify estrogen receptor status. Examination of the PAM50 cohort revealed a subset of PAM50 genes whose expression reflects cancer morphology. This work demonstrates the utility of deep learning-based image models in both clinical and research regimes, through its ability to uncover connections between visual morphology and genetic statuses.

The review looked at the issues of tumor heterogeneity in breast cancer. Tumor heterogeneity is classified according to the main feature demonstrating regional differences within a tumor (for example, heterogeneity of clinical manifestations, histological heterogeneity, heterogeneity of protein expression, etc.) and by tumor regions (differences between primary tumors and metastases, differences between cell clones within a single tumor node, etc.). Temporal heterogeneity is also distinguished, which manifests itself in the clonal evolution of tumor cells. The review covers the heterogeneity in the expression of four biomarkers from the gold standard for immunohistochemical staining of breast cancer: estrogen receptors, progesterone receptors, Her2/neu and Ki67 in primary tumor tissue and regional metastases. According to various studies, discordance in estrogen receptor status of primary tumor cells and metastases was observed with a frequency of 4 to 62%, progesterone receptors from 12 to 54%, Her2/neu from 0 to 24%, Ki67 from 4 to 39%. The results of studies of changes in the expression levels of individual markers in breast cancer metastases, as well as the heterogeneity of surrogate subtypes of tumor tissue in metastasis, are briefly described. Possible reasons for heterogeneity in the expression of key prognostic and predictive markers by primary tumor and metastatic cells, such as artificial factors at the preanalytic and analytic stages of the study, polyclonality of the primary tumor before metastasis, clonal evolution of tumor cells during metastasis, selection of tumor clones under the therapy are highlighted.

Objectives: This study sought to determine the presentation, treatment and outcomes of breast cancer among women in Cape Coast, Ghana.Design: Retrospective medical record reviewSetting: Cape Coast Teaching Hospital, Cape Coast, GhanaParticipants: Female breast cancer patientsInterventions: NoneMain outcome measures: Proportion of female breast cancer patients presenting with advanced disease.Results: Approximately 84% of women had a primary presentation of breast cancer, with metastatic disease present in 34% of patients. Surgical management mainly involved partial mastectomy (21.7%) and total mastectomy (78.6%), with the most common postoperative complications being surgical site infections (3.8%). Non-surgical management involved chemotherapy, radiation therapy and anti-estrogen therapy, with Stage 3 and 4 patients twofold more likely to receive neoadjuvant chemotherapy than earlier stages (OR= 2.0 95% CI (1.4, 3.0, p

BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8–20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with

The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2−/HR+), HER2-positive (HER2+)/HR+, and HER2−/HR-negative (HR−) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034–0.379; p

Background: We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer–specific and all-cause mortality. Methods: Among 8,932 women with stage I–III breast cancer identified in the Nurses' Health Study (NHS; 1980–2010) and NHSII (1991–2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer–specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis. Results: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer–specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09–1.63; Ptrend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10–1.45; Ptrend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08–1.40; Ptrend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04–1.38; Ptrend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07–1.42; Ptrend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. Conclusions: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer–specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. Impact: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis. See related commentary by McTiernan, p. 252

Background. According to the literature, BRCA1-associated breast cancer (BC) most often belongs to the triple negative (TNBC) molecular subtype. The data on the contribution of other molecular subtypes to this group of patients differ among different studies.The study objective is to evaluate the frequency of different tumor molecular subtypes in BC patients with BRCA1 gene mutation treated in N. N. Blokhin National Medical Research Center of Oncology in the period from 2017 to 2020.Materials and methods. The study included BC patients with a mutation in the BRCA1 gene (n = 209) identified as a result BRCA1 mutation screening of patients with BC. DNA diagnostics was carried out on blood samples of patients using the real-time polymerase chain reaction method. After analyzing the patients primary documentation clinical and morphological data were taken into account: the age of diagnosis, the stage of the disease, the results of immunohistochemical studies (estrogen receptor status, progesterone receptor status, HER2 expression, Ki-67 proliferation index). The assignment to the particular molecular tumour subtypes was performed according to estrogen receptor status, progesterone receptor status, HER2 status and Ki67 value.Results. Clinical and pathomorphological data of 209 patients with BRCA1-associated BC were analyzed. The age at diagnosis ranged from 23 to 72 years, the median age was 40 years, the mean age was 41.46 ± 9.82 years. BC associated with BRCA1 was found to be TNBC in 71.3 % and luminal B, HER2 negative (LumB–) in 19.1 % of the cases. Other tumour subtypes were much less common: luminal B, HER2 positive (LumB+) in 7.2 %, luminal A (LumA) in 1 % and HER2-positive (HER2+) in 1.4 % of the cases. The frequency of subtypes was estimated in different age groups (1st – patients 23–34 (n = 53), 2nd – 35–49 (n = 111), and 3rd – 50–72 (n = 45) years old). TNBC frequency was 81.1 % in the 1st group, 73.9 % in the 2nd and 53.4 % in the 3rd group; LumB– frequency was 15.1, 15.3 and 33.3 % respectively. Using the Fisher test it was shown that the differences in frequencies were statistically significant between groups 1st and 3 rd, as well as between groups 2 nd and 3 rd (p Conclusion. TNBC was the main molecular subtype in all age groups of BC patients with BRCA1 germinal mutation, TNBC frequency was lower in the older age group. LumB– subtype was also common in BRCA1-associated tumors especially in older women.

Different tumor-related factors have been proposed to assess the risk of disease progression and death in women undergoing neoadjuvant breast cancer chemotherapy. Recently, besides the classical pre-treatment clinical stage (CS) and post-treatment pathologic stage (PS), estrogen receptor status and histologic grade (CPS + EG score) and HER2 results (Neo-Bioscore) have also been added to this suite of staging systems, generating new scores. The present study aims to compare the performance of these four staging systems, namely CS, PS, CPS + EG and Neo-Bioscore, in the prognosis of breast cancer in women undergoing neoadjuvant chemotherapy. This study comprises a retrospective cohort study of female breast cancer patients diagnosed at the Brazilian National Cancer Institute, Brazil from January 2013 to December 2015. A descriptive analysis of patient characteristics was conducted, and Kaplan–Meier curves, a Cox proportional hazard analysis and Receiver Operating Characteristic (ROC) curves were developed according to the assessed staging system scores. A total of 803 patients were eligible for this study. Most were under 65 years old (88.0%), presented advanced tumors (clinical stage ≥ IIB 77.1%), with positive estrogen receptor (71.2%) and negative HER2 (75.7%) results. During the follow-up, 172 patients (21.4%) evolved to death. A statistical difference (p

Malignant pleural effusion is a common complication in metastatic breast cancer (MBC); however, changes in the pleural microenvironment are poorly characterized, especially with respect to estrogen receptor status. Histologically, MBC presents with increased microvessels beneath the parietal and visceral pleura, indicating generalized angiogenic activity. Breast cancer‐associated pleural fluid (BAPF) was collected and cultured with HUVECs to recapitulate the molecular changes in subpleural endothelial cells. The clinical progression of triple‐negative breast cancer (TNBC) is much more aggressive than that of hormone receptor‐positive breast cancer (HPBC). However, BAPF from HPBC (BAPF‐HP) and TNBC (BAPF‐TN) homogeneously induced endothelial proliferation, migration, and angiogenesis. In addition, BAPF elicited negligible changes in the protein marker of endothelial‐mesenchymal transition. Both BAPF‐HP and BAPF‐TN exclusively upregulated JNK signaling among all MAPKs in HUVECs. By contrast, the response to the JNK inhibitor was insignificant in Transwell and tube formation assays of the HUVECs cultured with BAPF‐TN. The distinct contribution of p‐JNK to endothelial angiogenesis was consequently thought to be induced by BAPF‐HP and BAPF‐TN. Due to increased angiogenic factors in HUVECs cultured with BAPF, vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor was applied accordingly. Responses to VEGFR2 blockade were observed in both BAPF‐HP and BAPF‐TN concerning endothelial migration and angiogenesis. In conclusion, the above results revealed microvessel formation in the pleura of MBC and the underlying activation of p‐JNK/VEGFR2 signaling. Distinct responses to blocking p‐JNK and VEGFR2 in HUVECs cultured with BAPF‐HP or BAPF‐TN could lay the groundwork for future investigations in treating MBC based on hormone receptor status., Current study evaluated the angiogenic response of HUVECs cultured with breast cancer‐associated pleural fluid (BAPF) obtained from hormone positive (HP) and triple negative (TN) breast cancer, respectively. Both BAPF‐HP and BAPF‐TN stimulated endothelial angiogenesis with upregulation of vascular endothelial growth factor receptor 2 (VEGFR2) and p‐JNK expressions. In contrast, application of p‐JNK inhibitor only showed efficacy in HUVECs cultured with BAPF‐HP, but not BAPF‐TN. Blockade of VEGFR2 signaling revealed potent inhibition on endothelial motility and angiogenesis induced by BAPF‐HP and BAPF‐TN.

Zhen Huang,* Qixing Tan,* Qinghong Qin, Qinguo Mo, Changyuan Wei Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinguo Mo; Changyuan WeiDepartment of Breast Surgery, Guangxi Medical University Cancer Hospital, 71 Hedi Road, Nanning 530021, People’s Republic of ChinaTel +86-771-5308593; + 86-771-5308593Fax +86-771-5312000Email qgmo135@263.net; weichangyuan@gxmu.edu.cnPurpose: The efficacy of primary site surgery in patients with de novo stage IV breast cancer remains controversial. However, few real-world studies have evaluated the benefits of local surgery on the primary site of stage IV breast cancer in China. The purpose of this study was to investigate the role of local surgery in the de novo stage IV breast cancer.Materials and Methods: Women with metastatic breast cancer at diagnosis were identified from Guangxi medical university cancer hospital (China) database from 2009 to 2017. The clinical and tumor features, surgical treatment, and survival rates were compared between surgical and non-surgical patients.Results: Two hundred forty-three patients were included, of whom 125 underwent primary site surgery. Patients who underwent surgery were more often had small primary tumors, fewer lymph node metastases, and had less visceral involvement. Patients in the surgery group had dramatically longer OS (median 35 vs 22 months, log-rank P=0.006). Stratified survival analysis showed that patients with bone metastasis alone or ≤ 3 metastasis benefit from surgery, while patients with visceral metastasis did not benefit from surgery. In multivariate analysis, surgical treatment, estrogen receptor status, progesterone receptor status and visceral metastases remained independent factors for survival.Conclusion: Surgical resection of the primary site can improve survival in selected de novo stage IV breast cancer patients.Keywords: stage IV breast cancer, surgery, survival

The oxytocin receptor (OXTR) plays an important role in childbirth, breastfeeding, and social interactions. There is emerging evidence that OXTR is associated with the breast cancer (BC) initiation and progression. However, the mechanisms leading to a change in its expression, the diagnostic or prognostic value of the receptor in BC are currently poorly understood. Here, we have evaluated the relative level of OXTR expression in BC samples (n=107), and also investigated the effect of estradiol on its expression in MCF-7 and MDA-MB-231 cells. The level of OXTR expression was significantly lower in breast tumor tissue than in normal tissue obtained from the same patient. The expression of OXTR was dependent on the status and expression of the estrogen receptor (ER): the level of OXTR mRNA was significantly lower in ER-negative BC samples compared to ER-positive BC samples. Moreover, OXTR expression was also lower in samples from patients with luminal subtype with a low value of ER expression (0-5 score according to the IHC assay, Allred scoring) compared with samples with high ER expression (6-8 score). In luminal BC, OXTR expression was associated with the HER2 expression level: the OXTR mRNA level was higher in tumors with a HER2 IHC score of 1+ as compared to cases with the HER2 expression score of 2+, 3+. We also showed that estradiol increased the level of OXTR mRNA in MCF-7 cells, but not in ER-negative MDA-MB-231 cells. These data indicate that changes in OXTR expression in BC tissues can be caused by increased ER expression. We found no association between OXTR and T or N stages and progesterone receptor expression.Retseptor oksitotsina (OXTR) igraet vazhnuiu rol' v protsessakh detorozhdeniia, grudnogo vskarmlivaniia i sotsial'nykh vzaimodeĭstviĭ. V poslednie gody poiavilis' dannye v pol'zu togo, chto OXTR sviazan s razvitiem i progressirovaniem raka molochnoĭ zhelezy (RMZh). Odnako mekhanizmy, privodiashchie k izmeneniiu ego ékspressii, diagnosticheskaia ili prognosticheskaia tsennost' retseptora pri RMZh na dannyĭ moment maloizuchenny. Poétomu my postavili tsel' otsenit' uroven' ékspressii OXTR v obraztsakh RMZh (n=107), a takzhe issledovat' vliianie éstradiola na ego ékspressiiu v kletkakh liniĭ MCF-7 i MDA-MB-231. Uroven' ékspressii OXTR byl znachitel'no nizhe v opukholevoĭ tkani molochnoĭ zhelezy, chem v normal'noĭ tkani, vziatoĭ ot togo zhe patsienta. Ékspressiia OXTR zavisela ot statusa i ékspressii éstrogenovogo retseptora (ER): uroven' mRNK OXTR byl dostoverno nizhe v obraztsakh ER-negativnogo RMZh po sravneniiu s obraztsami ER-pozitivnogo RMZh. Ékspressiia OXTR byla nizhe v obraztsakh patsientov s liuminal'nym RMZh pri nizkom znachenii ékspressii ER (0-5 ballov soglasno immunogistokhimicheskomu (IGKh) issledovaniiu, shkala Allred) po sravneniiu s obraztsami s vysokoĭ ékspressieĭ ER. Uroven' mRNK OXTR byl assotsiirovan s urovnem ékspressii HER2: uroven' mRNK OXTR byl znachitel'no povyshen v obraztsakh liuminal'nogo RMZh s urovnem ékspressii HER2 1 ball, soglasno IGKh issledovaniiu, po sravneniiu s opukholiami s vysokoĭ ékspressieĭ HER2 (2-3 balla). My takzhe pokazali, chto pod deĭstviem éstradiola uvelichivalsia uroven' mRNK OXTR v kletkakh MCF-7, no ne v ER-negativnykh kletkakh MDA-MB-231. Poluchennye dannye ukazyvaiut na to, chto izmenenie ékspressii OXTR v tkaniakh RMZh mozhet byt' vyzvano usileniem ékspressii ER. Sviazi OXTR so statusom T ili N opukholi i ékspressieĭ progesteronovogo retseptora vyiavleno ne bylo.

Introduction: Globally carcinoma breast is the leading cause of cancer death in women .Prognosis of such patients is related to a variety of Histomorphological features which includes, Histological grade, type, tumor size and lymph node metastases. Estrogen and progesterone receptors (ER, PR) and more recently, HER-2/neu have with increasing importance influenced the management of the malignancy. Materials and Methods: This study was carried out at tertiary care hospital which included 70 cases of breast cancer that we have reported at our department during a period from June 2012 to June 2014.Specimens were fixed overnight in 10% Neutral buffered formalin and processed as routine for H&E staining. Representative sections with tumour with adjacent normal breast tissue (internal control) were taken on Poly-L-Lysine coated slides and proceed for antigen retrieval, HRP Polymerization steps and than processed for ER, PR and HER-2/neu immuno-histochemical staining with respective antibody. Observation and Results: Maximum No. Of cases were in age group 5th and 6th decade with Invasive ductal carcinoma was predominately observed followed by invasive lobular carcinoma. Among 70 cases, 25 cases (35.71%) showing ER/PR+ HER 2- pattern which is predominant pattern in this study. While 23 cases (32.85%) showing Tripple negative pattern. Conclusion: most important cost effective, prognostic markers are estrogen receptor status, progesterone receptor status and HER2/neu status. Correlation of these marker status with clinical parameters helps in predicting the future treatment modalities and disease free survival for the patient in developing countries. Keywords: ER-Estrogen receptor, PR-Progesteron recptor, Immunohistochemistry.

Background Early and accurate assessment of the response to neoadjuvant chemotherapy offers the potential to optimize treatment to obtain improved responses. We aimed to predict the response to neoadjuvant chemotherapy using a second breast core needle biopsy after a median of 2 cycles of neoadjuvant chemotherapy. Methods We evaluated 805 consecutive patients undergoing neoadjuvant chemotherapy who had a second core needle biopsy between 2013 and 2017. The second core needle biopsy was performed after a median of 2 cycles of neoadjuvant chemotherapy. Pathologic response was evaluated after completion of all the chemotherapy cycles. Diagnostic values were compared and evaluated between the second core needle biopsy and contrast-enhanced magnetic resonance imaging in both the whole and the human epidermal growth factor receptor 2–positive populations. Results Overall, 653 patients were eligible and underwent a median of 6 chemotherapy cycles. The second core needle biopsy predicted residual breast cancer earlier than the final contrast-enhanced magnetic resonance imaging, with a greater positive predictive value (positive predictive value: 0.856 vs 0.802, P = .028). Multivariate analysis revealed that a estrogen receptor status, human epidermal growth factor receptor 2 positivity, findings on the final contrast-enhanced magnetic resonance imaging and the pathologic findings of the second core needle biopsy pathology were independent predictive factors for treatment response. The superiority in diagnostic value of a second core needle biopsy pathology in human epidermal growth factor receptor 2–positive patients was consistent with that in the whole population, with a positive predictive value of 0.785 (95% confidence interval: 0.707–0.847). The second core needle biopsy predicted the response to neoadjuvant chemotherapy as early as after 2 cycles, but the accuracy increased from 0.744 to 0.872 if the procedure was performed after more cycles (P = .002). Conclusion The second core needle biopsy predicted the response to neoadjuvant chemotherapy after 2 cycles quite well, especially in human epidermal growth factor receptor 2–positive patients. The ability of the prediction of response improved if the second biopsy was performed after 3 or 4 cycles.

Background We conducted this study to evaluate whether patients with T1a/b, node-negative (N−), human epidermal growth factor receptor 2-positive (HER2+) breast cancers benefited from adjuvant therapy, and explored better treatment strategies for these patients. Patients and Methods Patients with T1a/b, N−, HER2+ breast cancers during 2000 through 2004 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The Gray test was used to evaluate breast cancer-specific death (BCSD) and non-BCSD. To identify patients more suitable for chemotherapy, subgroup analyses were conducted according to tumor size and estrogen receptor (ER) status, and plots of hazard rate of death (HRD) were drawn to present the changes of BCSD. Results A total of 2940 patients with T1a/b, N−, HER2+ breast cancers were included; more patients in the T1b group received chemotherapy compared with the T1a group (65.18% vs. 29.30%; P Conclusion Chemotherapy, which is mainly decided by tumor size, fails to render survival benefits for patients with T1a/b, N−, HER2+ breast cancers. ER status, rather than tumor size, is important for clinicians to make adjuvant treatment decisions. The peak of BCSD occurs 2 to 5 years after diagnosis, and an at least 5-year follow-up is recommended for these patients.

Background Small-sized primary tumor does not always indicate a better prognosis. We hypothesized that very small primary breast tumors with extensive lymph node (LN) metastases represented an aggressive biologic behavior in stage IV disease. Materials and Methods Data between 2010 and 2015 were retrieved retrospectively from the Surveillance, Epidemiology, and End Results database with inclusion criteria of female sex, unilateral, metastatic, and T1/2 invasive ductal carcinoma. Primary study variables included T stage, N stage, grade, metastatic sites, number of involved sites, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Kaplan-Meier and adjusted Cox proportional hazards models with interaction terms were used. One-, 2- and 3-year breast cancer-specific mortality (BCSM) was examined according to tumor size. Results We identified 5,340 eligible patients with breast cancer. In multivariate analysis, race, age, grade, molecular subtype, surgery, brain metastases, and liver metastases were found to be independently associated with BCSM. For T1 tumors, the N0, N1, and N2+ groups had the same BCSM. In tumors smaller than 50 mm, the 1-, 2-, and 3-year BCSM did not decline with the decrease of tumor size. For triple-negative breast cancers (TNBCs), the T1a/T1bN2+ group had significantly worse BCSM than any other group did. Conclusion Patients with stage IV cancer with small-sized tumors may have BCSM as high as those with larger tumors. In TNBCs, very small tumors with severe LN involvement are associated with the worst BCSM. Continued efforts are needed to further investigate Ta1/T1bN2 + M1 TNBCs and individualize the treatment for affected patients. Implications for Practice This study revealed that for stage IV breast cancer, smaller primary tumors were not always associated with better breast cancer-specific mortality. This study illustrated that very small triple-negative breast cancers (TNBCs) with extensive regional lymph node involvement may be a surrogate for biologically aggressive disease. Because of poor prognosis of T1a/T1bN2+ TNBCs, there might be an urgent need of more individualized treatment for affected patients. Future correlative studies ought to focus on the genetic and molecular differences in Ta1/T1bN2+ TNBCs that contribute to the biological behavior. Clarification of the regulation mechanism of very small-sized primary TNBCs with metastatic outgrowth in nodes and distant sites will play an integral role in developing targeted therapies.

For newly diagnosed breast cancer, estrogen receptor status (ERS) is a key molecular marker used for prognosis and treatment decisions. During clinical management, ERS is determined by pathologists from immunohistochemistry (IHC) staining of biopsied tissue for the targeted receptor, which highlights the presence of cellular surface antigens. This is an expensive, time-consuming process which introduces discordance in results due to variability in IHC preparation and pathologist subjectivity. In contrast, hematoxylin and eosin (H&E) staining—which highlights cellular morphology—is quick, less expensive, and less variable in preparation. Here we show that machine learning can determine molecular marker status, as assessed by hormone receptors, directly from cellular morphology. We develop a multiple instance learning-based deep neural network that determines ERS from H&E-stained whole slide images (WSI). Our algorithm—trained strictly with WSI-level annotations—is accurate on a varied, multi-country dataset of 3,474 patients, achieving an area under the curve (AUC) of 0.92 for sensitivity and specificity. Our approach has the potential to augment clinicians’ capabilities in cancer prognosis and theragnosis by harnessing biological signals imperceptible to the human eye., Determination of estrogen receptor status (ERS) in breast cancer tissue requires immunohistochemistry, which is sensitive to the vagaries of sample processing and the subjectivity of pathologists. Here the authors present a deep learning model that determines ERS from H&E stained tissue, which could improve oncology decisions in under-resourced settings.

Background Surgery remains the mainstay of treatment for breast cancer spinal metastasis (BCSM) to relieve symptoms and improve the quality of life of BCSM patients. Therefore, it is important to effectively predict the prognosis of patients to determine whether they can undergo surgical operation. However, the prevalent methods for prognosis evaluation lack specificity and sensitivity for indicated malignancies like breast cancer because they are built on a relatively small number of heterogeneous types of primary tumors. The aim of the present study was to explore a novel predictive model based on the clinical, pathological and blood parameters obtained from BCSM patients before they received surgical intervention. Methods Altogether, 144 patients were included in this study. Univariate and multivariate analyses were performed to investigate the significance of preoperative parameters and identify independent factors for prognostic prediction of BCSM. A nomogram for survival prediction was then established and validated. Time-dependent ROC (TDROC) curves were graphed to evaluate the accuracy of the novel model vs other scoring systems including Tomita Score, revised Tokuhashi Score, modified Bauer Score and New England Spinal Metastasis Score. P values

Purpose of review HER2-positive (HER2+) breast cancer is clinically and biologically a heterogenous disease and not all patients benefit to the same extent from current anti-HER2 therapies. Recent findings Among HER2+ breast cancer, molecular intrinsic subtypes, PIK3CA mutation status, levels of HER2 gene/protein, immune infiltration, or intratumor heterogeneity modulate HER2-treatment sensitivity. HER2-enriched carcinomas, with high levels of HER2 and tumor-infiltrating lymphocytes (TILs) are highly sensitive to anti-HER2 therapies, regardless of chemotherapy. Luminal A/B tumors are more estrogen receptor-dependent than HER2-dependent, harbor higher rates of PIK3CA mutations, and are less responsive to anti-HER2 treatment. HER2 intratumoral heterogeneity that exists in approximately 10% of HER2+ disease may also cause treatment resistance. Early changes occur during neoadjuvant anti-HER2 therapy that can predict response. Importantly, HER2 expression is not a binary but rather a continuous variable. Overall, 34-63% of HER2-negative breast cancers express HER2, and HER2-low tumors have become a new entity, for which novel-targeted therapies may be effective. Summary Although much of what is discussed currently remains investigational, it is clear that HER2+ breast cancer is a complex disease comprising different entities. Future strategies to escalate or de-escalate treatment in early-stage HER2+ disease should consider other biomarkers beyond HER2 and estrogen receptor status, including intrinsic subtype, HER2 levels, and TILs; and evaluate different treatment strategies among patients with estrogen receptor-positive/HER2+ and estrogen receptor-negative/HER2+ diseases.

This study aimed to develop a model that fused multiple features (multi-feature fusion model) for predicting metachronous distant metastasis (DM) in breast cancer (BC) based on clinicopathological characteristics and magnetic resonance imaging (MRI). A nomogram based on clinicopathological features (clinicopathological-feature model) and a nomogram based on the multi-feature fusion model were constructed based on BC patients with DM (n=67) and matched patients (n=134) without DM. DM was diagnosed on average (17.31±13.12) months after diagnosis. The clinicopathological-feature model included seven features: reproductive history, lymph node metastasis, estrogen receptor status, progesterone receptor status, CA153, CEA, and endocrine therapy. The multi-feature fusion model included the same features and an additional three MRI features (multiple masses, fat-saturated T2WI signal, and mass size). The multi-feature fusion model was relatively better at predicting DM. The sensitivity, specificity, diagnostic accuracy and AUC of the multi-feature fusion model were 0.746 (95% CI: 0.623-0.841), 0.806 (0.727-0.867), 0.786 (0.723-0.841), and 0.854 (0.798-0.911), respectively. Both internal and external validations suggested good generalizability of the multi-feature fusion model to the clinic. The incorporation of MRI factors significantly improved the specificity and sensitivity of the nomogram. The constructed multi-feature fusion nomogram may guide DM screening and the implementation of prophylactic treatment for BC.