We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of ...this study was to quantify the extent of tumor load reduction achieved by TAS.
International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load.
A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3–7) nodes, two (IQR 1–4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10–17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%.
TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.
•Tailored axillary surgery is a novel concept for clinically node-positive breast cancer•Tailored axillary surgery selectively removes positive lymph nodes•Tailored axillary surgery is much less radical than axillary dissection•Tailored axillary surgery removes the clipped node in the vast majority of patients
The presence of circulating tumor cells (CTC) in the peripheral blood of cancer patients has been described for various solid tumors and their clinical relevance has been shown. CTC detection based ...on the analysis of epithelial antigens might be hampered by the genetic heterogeneity of the primary tumor and loss of epithelial antigens. Therefore, we aimed to identify new gene markers for the PCR-based detection of CTC in female cancer patients.
Gene expression of 38 cancer cell lines (breast, ovarian, cervical and endometrial) and of 10 peripheral blood mononuclear cell (PBMC) samples from healthy female donors was measured using microarray technology (Applied Biosystems). Differentially expressed genes were identified using the maxT test and the 50% one-sided trimmed maxT-test. Confirmatory RT-qPCR was performed for 380 gene targets using the AB TaqMan® Low Density Arrays. Then, 93 gene targets were analyzed using the same RT-qPCR platform in tumor tissues of 126 patients with primary breast, ovarian or endometrial cancer. Finally, blood samples from 26 healthy women and from 125 patients (primary breast, ovarian, cervical, or endometrial cancer, and advanced breast cancer) were analyzed following OncoQuick enrichment and RNA pre-amplification. Likewise, hMAM and EpCAM gene expression was analyzed in the blood of breast and ovarian cancer patients. For each gene, a cut-off threshold value was set at three standard deviations from the mean expression level of the healthy controls to identify potential markers for CTC detection.
Six genes were over-expressed in blood samples from 81% of patients with advanced and 29% of patients with primary breast cancer. EpCAM gene expression was detected in 19% and 5% of patients, respectively, whereas hMAM gene expression was observed in the advanced group (39%) only. Multimarker analysis using the new six gene panel positively identified 44% of the cervical, 64% of the endometrial and 19% of the ovarian cancer patients.
The panel of six genes was found superior to EpCAM and hMAM for the detection of circulating tumor cells in the blood of breast cancer, and they may serve as potential markers for CTC derived from endometrial, cervical, and ovarian cancers.
Purpose
Chemoprevention with a selective estrogen receptor modulator (tamoxifen or raloxifene) is a non-surgical option offered to high-risk women to reduce the risk of breast cancer. The evidence ...for tamoxifen benefit is based on trials conducted among predominantly postmenopausal women from the general population and on studies of contralateral breast cancer in women with a pathogenic variant (mutation hereafter) in
BRCA1
or
BRCA2
. Tamoxifen has not been assessed as a primary prevention agent in women with an inherited
BRCA
mutation.
Methods
We conducted a prospective analysis of tamoxifen chemoprevention and the risk of breast cancer in women with a
BRCA1
or
BRCA2
mutation. Data on tamoxifen (and raloxifene) use was collected by questionnaire and updated biennially. Information on incident cancers was collected by self-report and was confirmed by medical record review. In a matched analysis, we estimated the hazard ratio (HR) and 95% confidence intervals (CI) for developing a first primary breast cancer associated with tamoxifen or raloxifene use, using Cox proportional hazards analysis.
Results
There were 4578 unaffected women in the cohort, of whom 137 reported tamoxifen use (3%), 83 reported raloxifene use (2%) and 12 used both drugs (0.3%). Women who used tamoxifen or raloxifene were matched 1:3 with women who used neither drug on year of birth, country of residence, year of study entry and gene (
BRCA1
or
BRCA2
). We generated 202 matched pairs. After a mean follow-up of 6.8 years, there were 22 incident breast cancers diagnosed among tamoxifen/raloxifene users (10.9% of users) and 71 cases diagnosed among non-users (14.3% of non-users; HR = 0.64; 95% CI 0.40–1.03;
P
= 0.07).
Conclusion
Chemoprevention may be an effective risk-reduction option for
BRCA
mutation carriers, but further studies with longer follow-up are necessary.
Purpose IMpassion130 led to the approval of atezolizumab plus nab-paclitaxel as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative, PD-L1 immune-cell ...positive breast cancer (BC) by the European Medicines Agency (EMA). The objective of the present study was to investigate the implementation, safety and efficacy of this combination in the initial phase after approval. Methods A retrospective data analysis including all BC patients who received atezolizumab and nab-paclitaxel between 1.1.2019 and 31.10.2020 at the Department of Obstetrics and Gynecology and the Department of Medicine 1, respectively, at the Medical University of Vienna, Austria, was performed. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Maier product-limit method. Owing to the retrospective nature of this study, all statistics must be considered exploratory. Results In total 20 patients were included in the study. Median follow-up was 7.1 months (IQR 5.2-9.1). Median PFS was 3.0 months (SE = .24; 95% CI 2.5; 3.5). Median OS was 8.94 months (SE = 2.34, 95%CI 4.35; 13.53). No new safety signals were observed. Conclusion The present study showed a considerably shorter PFS (3.0 vs. 7.5 months) and OS (8.94 vs. 25.0 months) than IMpassion130 putatively owing to the use of atezolizumab in later treatment lines, more aggressive tumors and a study population with higher morbidity compared to the pivotal trial. Keywords: Breast cancer, Atezolizumab, Real-world, Progression-free survival, Overall survival
For women at high risk of developing ovarian cancer, it is important to provide an accurate recommendation for the optimal age for preventive surgery in order to maximize the preventative effect ...while delaying symptoms associated with early surgical menopause. The goal of the current study was to estimate age-specific incidence rates of ovarian cancer among women with a BRCA1 or BRCA2 mutation.
From our international registry, we identified 5689 women with no previous diagnosis of ovarian or fallopian tube cancer or preventive oophorectomy. Women were followed from the date of completion of the baseline questionnaire until either a diagnosis of ovarian or fallopian tube cancer, prophylactic oophorectomy, death or last follow-up. The annual and cumulative incidence rates of ovarian cancer were estimated.
Over a mean follow-up period of 4.7 years (ranges 0–22.6), 195 incident ovarian or fallopian tube cancers were diagnosed (169 86% ovarian cancers, 22 11% fallopian tube cancers and four 2% cancers that involved both the ovaries and fallopian tubes). Of these, 45 (23%) cancers were diagnosed at preventive surgery (occult cancers). The cumulative risk of ovarian cancer to age 80 was 49% for BRCA1 and 21% for BRCA2 mutation carriers. The mean age at diagnosis was 51.3 years (ranges 33–84) among women with a BRCA1 mutation and 61.4 years (ranges 44–80) among women with a BRCA2 mutation.
Based on a cumulative risk of 0.55% to age 35 for BRCA1 mutation carriers and of 0.56% to age 45 for BRCA2 mutation carriers, we recommend bilateral salpingo-oophorectomy before age 40, but ideally by age 35, for women with a BRCA1 mutation and by age 45 for those with a BRCA2 mutation to maximize prevention and to minimize adverse effects.
•BRCA mutation carriers face high lifetime risks of ovarian cancer.•A proportion of ovarian cancers are diagnosed at the time of preventive surgery.•Bilateral salpingo-oophorectomy (BSO) before age 40 (but ideally by age 35) for women with a BRCA1 mutation•BSO by age 45 for women with a BRCA2 mutation
Background Residual fibroglandular breast tissue (RFGT) following a mastectomy is associated with the remaining of occult breast cancer at the time of mastectomy as well as an increased local ...recurrence risk thereafter. Despite its oncologic implications, data on measures to prevent RFGT are lacking. Therefore, in a first step knowledge of risk factors for RFGT is of uttermost importance in order to allow identification of patients at risk and subsequently adaption of the surgical treatment and potentially prevention of RFGT a priori. Methods We performed a systematic literature review in PubMed using the MESH terms residual fibroglandular breast tissue, residual breast tissue, mastectomy and risk factor followed by a retrospective data analysis including all patients with a mastectomy treated at the Department of Obstetrics and Gynecology of the Medical University of Vienna, Austria, between 01.01.2015 and 26.02.2020 in order to identify risk factors of RFGT following a mastectomy. The primary aim of the study was to assess a potential difference in RFGT volume between the different types of mastectomy. The secondary objectives of the study were to identify other potential risk factors for RFGT as well as to compare the skin and subcutaneous fat tissue thickness pre- to postoperatively. Results Significantly higher RFGT volumes were observed following a nipple-sparing mastectomy (NSM) compared to a skin-sparing mastectomy (SSM) and radical mastectomy (RME) (p < .001). Furthermore, RFGT volume was significantly associated with the variables: reconstruction (p = .012), acellular dermal matrix (ADM) or mesh (p = .031), patient age (p = .022), preoperative fibroglandular tissue (FGT) volume (p = .012) and preoperative whole breast volume (including the skin envelope and nipple-areola-complex) (p = .030). The reduction in the postoperative compared to preoperative skin envelope thickness measured medially and laterally reached statistical significance in the NSM-cohort (medial p < .001, lateral p = .001) and showed a numerical difference in the RME and SSM-cohort. Conclusion Mastectomy type, reconstruction, ADM or mesh, patient age, preoperative FGT volume and whole breast volume were identified as risk factors for RFGT in univariable analysis. The observed reduction in the post- compared to preoperative skin envelope thickness should be avoided considering the known associated increase in risk for ischemic complications. Keywords: Residual fibroglandular breast tissue, Mastectomy, Risk factor, Nipple-sparing mastectomy
Neoadjuvant chemotherapy (NaCT) and neoadjuvant endocrine therapy (NET) can reduce pre-operative tumour burden in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor ...2 (HER2)-negative early-stage breast cancer. This prospective translational study assessed the ability of a 12-gene molecular score (MS; EndoPredict®) to predict response to NaCT or NET within the ABCSG-34 trial.
Hormone receptor (HR)-positive, HER2-negative samples from patients in the ABCSG-34 randomized phase II trial were selected and EndoPredict testing was performed to generate a 12-gene MS. ABCSG-34 patients were assigned to receive either NaCT or NET based on menopausal status, HR expression, grade and Ki67. Response was measured by residual cancer burden (RCB).
Patients selected for NaCT generally had high-risk disease by 12-gene MS (125/134), while slightly more patients treated with NET had low-risk disease (44/83). Low-risk NaCT-treated and high-risk NET-treated tumours responded poorly (NPV 100% 95% CI 66.4%–100% and NPV 92.3% 95% CI 79.1%–98.4%, respectively. The 12-gene MS significantly predicted treatment response for NaCT (AUC 0.736 95% CI 0.63–0.84) and NET (AUC 0.726 95% CI 0.60–0.85).
The 12-gene MS predicted RCB after treatment with neoadjuvant therapies for patients with HR-positive, HER2-negative early-stage breast cancer. Tumours with low MS were unlikely to benefit from NaCT, whereas a high MS predicted resistance to NET. This additional biologic information can aid personalized treatment selection in daily practice and builds a strong rationale to use EndoPredict in biomarker-driven studies in the neoadjuvant setting.
•A 12-gene molecular score predicted response to pre-operative neoadjuvant therapy.•Low-score breast tumours were unlikely to respond to neoadjuvant chemotherapy.•Breast tumours with high scores were resistant to neoadjuvant endocrine therapy.
To determine whether adjuvant tamoxifen treatment for breast cancer (BC) is associated with reduced contralateral breast cancer (CBC) risk for BRCA1 and/or BRCA2 mutation carriers.
Analysis of pooled ...observational cohort data, self-reported at enrollment and at follow-up from the International BRCA1, and BRCA2 Carrier Cohort Study, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer, and Breast Cancer Family Registry. Eligible women were BRCA1 and BRCA2 mutation carriers diagnosed with unilateral BC since 1970 and no other invasive cancer or tamoxifen use before first BC. Hazard ratios (HRs) for CBC associated with tamoxifen use were estimated using Cox regression, adjusting for year and age of diagnosis, country, and bilateral oophorectomy and censoring at contralateral mastectomy, death, or loss to follow-up.
Of 1,583 BRCA1 and 881 BRCA2 mutation carriers, 383 (24%) and 454 (52%), respectively, took tamoxifen after first BC diagnosis. There were 520 CBCs over 20,104 person-years of observation. The adjusted HR estimates were 0.38 (95% CI, 0.27 to 0.55) and 0.33 (95% CI, 0.22 to 0.50) for BRCA1 and BRCA2 mutation carriers, respectively. After left truncating at recruitment to the cohort, adjusted HR estimates were 0.58 (95% CI, 0.29 to 1.13) and 0.48 (95% CI, 0.22 to 1.05) based on 657 BRCA1 and 426 BRCA2 mutation carriers with 100 CBCs over 4,392 person-years of prospective follow-up. HRs did not differ by estrogen receptor status of the first BC (missing for 56% of cases).
This study provides evidence that tamoxifen use is associated with a reduction in CBC risk for BRCA1 and BRCA2 mutation carriers. Further follow-up of these cohorts will provide increased statistical power for future prospective analyses.
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