Project description:BackgroundNeoadjuvant chemotherapy (NAC) is standard for many females with breast cancer (FBC). The efficacy of NAC in male breast cancer (MaBC) is unclear. The aim of this study was to compare proportions of pathologic complete response (pCR) between MaBC and FBC by tumor subtype (TS).MethodsMaBC and FBC treated with NAC between 2010 and 2016, with known TS, were evaluated from the National Cancer Database. Proportions of pCR (ypT0/Tis ypN0) were compared between sexes within TS by Fisher test. Multivariable logistic regression assessed the independent association of sex with pCR. Overall survival (OS) was estimated by Kaplan-Meier.ResultsA total of 385 MaBC and 68,065 FBC were included. Median time from initiation of NAC to surgery was 143 days in MaBC and 148 days in FBC. Proportions of pCR in MaBC and FBC by TS were: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-): 4.9% vs 9.7%, p = .01; HR+/HER2+: 16.1% vs 33.6%, p < .001; HR-/HER2+: 44.0% vs 53.2%, p = .42; and HR-/HER2-: 21.4% vs 32.1%, p = .18, respectively. FBC had twice the odds of pCR than MaBC (adjusted odds ratio, 2.0; 95% CI, 1.5-2.8; p < .001). Five-year OS for MaBC with pCR vs not was 90% vs 64.7%; p = .02. Five-year OS for FBC with pCR vs not was 91.9% vs 75.3%; p < .01.ConclusionsProportions and odds of pCR to NAC were numerically lower in MaBC compared with FBC for each TS and statistically significant for HR+/HER2- and HR+/HER2+. The independent association of sex with pCR was confirmed in multivariable analysis. pCR is prognostic in both MaBC and FBC.
Project description:In the last few decades, neoadjuvant therapy for breast cancer has gained considerable therapeutic importance. Despite extensive clinical investigations, it has not yet been clarified whether neoadjuvant therapy would result in improved survival in comparison with the standard adjuvant setting in any subgroups of patients with breast cancer. Chemotherapy is especially effective in the treatment of endocrine insensitive tumors, and such ther-apeutic benefit can be assumed for patients with triple-negative, or hormone receptor-negative and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, dose escalation, modification of the therapeutic regimens according to early tumor response, as well as the optimal sequence of administration are still matters of debate. There is a current debate between clinical experts regarding the concomitant and sequential administration of carboplatin and capecitabine, respectively, as part of the standard neoadjuvant treatment, as well as the use of bevacizumab, as part of the preoperative treatment. In case of HER2 positive tumors, an anti-HER2 agent can be administered as part of the preoperative treatment, and according to preliminary clinical data, dual HER2 blockade can also be reasonable. Further, chemotherapy-free regimens can be justified in highly endocrine sensitive tumors, while immune modulating agents may also gain particular importance in the case of certain subtypes of breast cancer. Several small-molecule targeted therapies are under clinical investigation and are expected to provide new neoadjuvant treatment options. However, novel, more predictive biomarkers are required for further evaluation of the neoadjuvant therapies, as well as the effect of novel targeted agents intended to be incorporated into neoadjuvant therapy.
Project description:Approximately one quarter of patients with breast cancer demonstrate amplification of the human epidermal receptor type 2 (HER2) gene, the expression of which is associated with a relatively poor prognosis independent of other clinical and pathologic variables. Trastuzumab, a humanized recombinant monoclonal antibody specifically directed against the HER2 receptor, has been shown to be biologically active and of considerable clinical utility in HER2-positive breast cancer patients. Neoadjuvant chemotherapy has been used in breast cancer to downstage the tumor and increase the opportunity for breast-conserving surgery. Preoperative chemotherapy can also serve as an in vivo testing of chemotherapy sensitivity. Additionally, a pathologic complete response is usually a surrogate marker of disease-free survival. Following the successful use of trastuzumab in the metastatic and adjuvant settings, many clinical trials have recently reported the successful use of anti-HER2 therapy in combination with different chemotherapy regimens in the neoadjuvant setting with a significantly higher pathologic complete response. With the recent introduction of new anti-HER2 drugs, interest has shifted toward dual HER2 blockade. Two such studies were recently reported, both showing a significant advantage of dual anti-HER2 therapy using lapatinib or pertuzumab in addition to trastuzumab and chemotherapy. However, several key questions need to be investigated further, such as the preferred combination chemotherapy and the optimal duration of trastuzumab in patients who achieve a pathologic complete response following preoperative chemotherapy with trastuzumab. These issues and others are discussed in this review.
Project description:Neoadjuvant chemotherapy has the advantage of converting unresectable breast tumors to resectable tumors and allowing more conservative surgery in some mastectomy candidates. Chemotherapy agents, including taxanes, which are recommended in the adjuvant setting, are also considered in the neoadjuvant setting. Here, we review studies of nab-paclitaxel as a neoadjuvant treatment for patients with breast cancer. PubMed and conference or congress proceedings were searched for clinical studies of nab-paclitaxel in the neoadjuvant treatment of breast cancer. We also searched ClinicalTrials.gov for ongoing trials of nab-paclitaxel as a neoadjuvant agent in breast cancer. Twenty studies of nab-paclitaxel in the neoadjuvant setting were identified. In addition to reviewing key efficacy and safety data, we discuss how each trial assessed response, focusing on pathologic complete response and residual cancer burden scoring. Safety profiles are also reviewed. nab-Paclitaxel demonstrated antitumor activity and an acceptable safety profile in the neoadjuvant treatment of breast cancer. Ongoing and future trials will further evaluate preoperative nab-paclitaxel in breast cancer, including in combination with many novel immunological targeted therapies.
Project description:Breast imaging techniques are used to assess the tumor response to neoadjuvant treatment (NAT), which is increasingly one of the preferred therapeutic options and increases the rate of breast conservation for breast cancer. Herein, we report a case in which a woman was diagnosed with invasive ductal carcinoma in the left breast and received NAT before surgery. Automated breast ultrasound (AB US) was regularly performed before and during the NAT to evaluate the tumor response to NAT by measuring diameter changes and volume reductions of the tumor. Images showed that the tumor size was significantly reduced and disappeared after 7 cycles of NAT, except for macrocalcification. Postoperative histopathological examination confirmed that there were no residual tumor cells. We found that AB US overcame the limitations of handheld US, such as operator dependence, poor reproducibility and limited field of view, and can be an alternative modality to assess the tumor response of NAT in the absence of magnetic resonance imaging (MRI) instruments.
Project description:Tumor relapse as a consequence of chemotherapy resistance is a major clinical challenge in advanced stage breast tumors. To identify processes associated with poor clinical outcome, we took a mass spectrometry-based proteomic approach and analyzed a breast cancer cohort of 113 formalin-fixed paraffin-embedded samples. Proteomic profiling of matched tumors before and after chemotherapy, and tumor-adjacent normal tissue, all from the same patients, allowed us to define eight patterns of protein level changes, two of which correlate to better chemotherapy response. Supervised analysis identified two proteins of proline biosynthesis pathway, PYCR1 and ALDH18A1, that were significantly associated with resistance to treatment based on pattern dominance. Weighted gene correlation network analysis of post-treatment samples revealed that these proteins are associated with tumor relapse and affect patient survival. Functional analysis showed that knockdown of PYCR1 reduced invasion and migration capabilities of breast cancer cell lines. PYCR1 knockout significantly reduced tumor burden and increased drug sensitivity of orthotopically injected ER-positive tumor in vivo, thus emphasizing the role of PYCR1 in resistance to chemotherapy.
Project description:Breast cancer is the most prevalent malignant disease in women worldwide. Traditionally, surgical tumour resection was the primary step within the treatment algorithm of early stage disease; systemic therapy in order to reduce the rate of systemic recurrences followed. National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration of chemotherapy was equally effective. This study therefore established neoadjuvant chemotherapy as a valid treatment option, as the breast conservation rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and taxanes yield pathological complete response (pCR) rates of around 20%, with higher efficacy observed in triple-negative tumours. The antibody trastuzumab is the first targeted agent established in neoadjuvant regimens for the treatment of Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification.
Project description:Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.
Project description:Pre-surgical treatments in patients with early breast cancer allows a direct estimation of treatment efficacy, by comparing the tumor and the treatment. Patients who achieve a pathological complete response at surgery have a better prognosis, with lower risk of disease recurrence and death. Hence, clinical research efforts have been focusing on high-risk patients with residual disease at surgery, who may be "salvaged" through additional treatments administered in the post-neoadjuvant setting. In the present review, we aim to illustrate the development and advantages of the post-neoadjuvant setting, and to discuss the available strategies for patients with early breast cancer, either approved or under investigation. This review was written after literature search on main scientific databases (e.g., PubMed) and conference proceedings from major oncology conferences up to 1 August 2022. T-DM1 and capecitabine are currently approved as post-neoadjuvant treatments for patients with HER2-positive and triple-negative breast cancer, respectively, with residual disease at surgery. More recently, other treatment strategies have been approved for patients with high-risk early breast cancer, including the immune checkpoint inhibitor pembrolizumab, the PARP inhibitor olaparib and the CDK 4/6 inhibitor abemaciclib. Novel agents and treatment combinations are currently under investigation as promising post-neoadjuvant treatment strategies.