Breast最新文献

Primary tumors with a mixed invasive breast carcinoma of no-special type (IBC-NST) and invasive lobular cancer (ILC) histology are present in approximately five percent of all patients with breast cancer and are understudied at the metastatic level. Here, we characterized the histology of metastases from two patients with primary mixed IBC-NST/ILC from the postmortem tissue donation program UPTIDER (NCT04531696). The 14 and 43 metastatic lesions collected at autopsy had morphological features and E-cadherin staining patterns consistent with pure ILC. While our findings still require further validation, they may challenge current clinical practice and imaging modalities used in these patients.

To determine the changes in surveillance category by adding a polygenic risk score based on 311 breast cancer (BC)-associated variants (PRS₃₁₁), questionnaire-based risk factors and breast density on personalized BC risk in unaffected women from Dutch CHEK2 c.1100delC families.

In total, 117 unaffected women (58 heterozygotes and 59 non-carriers) from CHEK2 families were included. Blood-derived DNA samples were genotyped with the GSAMDv3-array to determine PRS₃₁₁. Lifetime BC risk was calculated in CanRisk, which uses data from the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). Women, were categorized into three surveillance groups.

The surveillance advice was reclassified in 20 (34.5%) heterozygotes and 21 (35.6%) non-carriers after adding PRS₃₁₁. Including questionnaire-based risk factors resulted in an additional change in 11 (20.0%) heterozygotes and 8 (15.1%) non-carriers; and a sub-analysis showed that adding breast density on top shifted another 9 (23.1%) heterozygotes and 5 (27.8%) non-carriers. Overall, the majority of heterozygotes were reclassified to a less intensive surveillance, while non-carriers would require intensified surveillance.

The addition of PRS₃₁₁, questionnaire-based risk factors and breast density to family history resulted in a more personalized BC surveillance advice in CHEK2-families, which may lead to more efficient use of surveillance.

Introduction

The impact of distinct estrogen receptor (ER) and progesterone receptor (PR) expression patterns on tumor behavior and treatment outcomes within HER2-positive breast cancer is not fully explored. This study aimed to comprehensively examine the clinical differences among patients with HER2-positive breast cancer harboring distinct ER and PR expression patterns in the neoadjuvant setting.

Methods

This retrospective analysis included 871 HER2-positive breast patients treated with neoadjuvant therapy at our hospital between 2011 and 2022. Comparisons were performed across the three hormone receptor (HR)-specific subtypes, namely the ER-negative/PR-negative/HER2-positive (ER-/PR-/HER2+), the single HR-positive (HR+)/HER2+, and the triple-positive breast cancer (TPBC) subtypes.

Results

Of 871 patients, 21.0% had ER-/PR-/HER2+ tumors, 33.6% had single HR+/HER2+ disease, and 45.4% had TPBC. Individuals with single HR+/HER2+ tumors and TPBC cases demonstrated significantly lower pathological complete response (pCR) rates compared to those with ER-/PR-/HER2+ tumors (36.9% vs. 24.3% vs. 49.2%, p < 0.001). Multivariate analysis confirmed TPBC as significantly associated with decreased pCR likelihood (OR = 0.42, 95%CI 0.28–0.63, p < 0.001). Survival outcomes, including disease-free survival (DFS) and overall survival (OS), showed no significant differences across HR-specific subtypes in the overall patient population. However, within patients without anti-HER2 therapy, TPBC was linked to improved DFS and a trend towards better OS.

Conclusions

HER2-positive breast cancer exhibited three distinct HR-specific subtypes with varying clinical manifestations and treatment responses. These findings suggest personalized treatment strategies considering ER and PR expression patterns, emphasizing the need for further investigations to unravel molecular traits underlying HER2-positive breast cancer with distinct HR expression patterns.

Background

When taken as prescribed, endocrine therapy is effective in reducing risk of recurrence and mortality in the treatment of patients with breast cancer. However, treatment side effects can act as a barrier to medication adherence. Existing research has not identified any specific side effects as consistent predictors of nonadherence. Our aim was to explore the influence of symptom clusters on self-reported adherence in patients with breast cancer.

Methods

A cross-sectional online survey was conducted, including patients with breast cancer currently or previously prescribed endocrine therapy (N = 1051). This included measures of self-reported endocrine therapy adherence and common symptoms among this population (insomnia, depression, anxiety, fatigue, musculoskeletal, and vasomotor symptoms).

Results

Unintentional nonadherence was higher than intentional nonadherence (50.8 % vs 31.01 %). The most troublesome symptom was insomnia (73.83 % displayed probable insomnia disorder). K-means cluster analysis identified 2 symptom clusters: overall High symptoms, and overall Low symptoms. Participants in the Low symptoms cluster were significantly more likely to be classed as adherent based on unintentional and intentional items.

Conclusions

Nonadherence was high in the current sample, and significantly more likely in participants reporting overall severe symptoms. Clinicians should be aware of the scale of common side effects and facilitate open conversation about potential barriers to adherence. Follow-up care should include assessment of common symptoms and signpost patients to appropriate support or treatment when required. Future research should explore potential for a central symptom to act as a target for intervention, to relieve overall side effect burden and facilitate better medication adherence.

Objective

This study aims to evaluate the response to and surgical benefits of neoadjuvant endocrine therapy (NET) in ER+/HER2-breast cancer patients who are clinically high risk, but genomic low risk according to the 70-gene signature (MammaPrint).

Methods

Patients with ER+/HER2-invasive breast cancer with a clinical high risk according to MINDACT, who had a genomic low risk according to the 70-gene signature and were treated with NET between 2015 and 2023 in our center, were retrospectively analyzed. RECIST 1.1 criteria were used to assess radiological response using MRI or ultrasound. Surgical specimens were evaluated to assess pathological response. Two breast cancer surgeons independently scored the eligibility of breast conserving therapy (BCS) pre- and post- NET.

Results

Of 72 included patients, 23 were premenopausal (100% started with tamoxifen of which 4 also received OFS) and 49 were postmenopausal (98% started with an aromatase inhibitor). Overall, 8 (11%) showed radiological complete response. Only 1 (1.4%) patient had a pathological complete response (RCB-0) and 68 (94.4%) had a pathological partial response (RCB-1 or RCB-2). Among the 26 patients initially considered for mastectomy, 14 (53.8%) underwent successful BCS. In all 20 clinical node-positive patients, a marked axillary lymph node was removed to assess response. Four out of 20 (20%) patients had a pathological complete response of the axilla.

Conclusion

The study showed that a subgroup of patients with a clinical high risk and a genomic low risk ER+/HER2-breast cancer benefits from NET resulting in BCS instead of a mastectomy. Additionally, NET may enable de-escalation in axillary treatment.

Background

Breast cancer (BC) is the most incident tumor and, consequently, any new intervention can potentially promote a considerable budget impact if incorporated. Cost-effectiveness (CE) studies assist in the decision-making process but may be influenced by the country's perspective of analysis and pharmaceutical industry funding.

Methods

A systematic review of Medline, Scopus, and Web of Science from January 1st, 2012 to July 8th, 2022 was conducted to identify CE studies of tumor-targeted systemic-therapies for advanced BC. Articles without incremental cost-effectiveness ratio calculations were excluded. We extracted information on the country and class of drug studied, comparator type, authors’ conflicts of interest (COI), pharmaceutical industry funding, and authors' conclusions.

Results

71 studies comprising 204 CE assessments were included. The majority of studies were from the United States and Canada (44%), Asia (32%) and Europe (20%). Only 8% were from Latin America and none from Africa. 31% had pharmaceutical industry funding. The most studied drug classes were cyclin-dependent-kinase inhibitors (29%), anti-HER2 therapy (23%), anti-PD(L)1 (11%) and hormone therapy (11%). Overall, 34% of CE assessments had favorable conclusions. Pharmaceutical industry-funded articles had a higher proportion of at least one favorable conclusion (82% vs. 24%, p-value<0.001), European countries analyzed (45% vs. 9%, p-value = 0.003), and CE assessments with same class drug comparators (56% vs. 33%, p-value = 0.004).

Conclusions

Breast cancer CE literature scarcely represents low-and-middle-income countries' perspectives and is influenced by pharmaceutical industry funding which targets European countries', frequently utilizes comparisons within same-drug class, and is more likely to have favorable conclusions.

Background

Optimizing chemotherapy to achieve disease and symptoms control is a noteworthy purpose in advanced breast cancer (ABC). We reported the activity and quality of life of a phase II study, comparing metronomic regimen with standard schedule as first line chemotherapy for ABC.

Methods

Patients with HER2 negative ABC were randomized to non-pegylated liposomal doxorubicin (NPLD, 60 mg/m2 every 3 weeks) and cyclophosphamide (CTX, 600 mg/m2 every 3 weeks) (Arm A) or NPLD (20 mg/m2 day, on day 1, 8 and 15 every 4 weeks) and metronomic daily oral CTX 50 mg (ARM B). Primary end-points were overall response rate (ORR) and quality of life, secondary progression-free survival (PFS), overall survival (OS) and toxicity.

Results

From August 2012 to December 2017, 121 patients were enrolled, 105 evaluable. Median follow-up was 21.3 months. Most patients had hormone receptor positive. ORR was 43 % in arm A and 50 % in arm B. Median PFS was 8.9 months in arm A and 6,4 months in arm B. There was no difference in OS. Total score was not clinically different between the two arms. Grade 4 neutropenia was observed in 12 patients and 16 patients respectively; alopecia G2 in 41 % (77 %) vs 14 (27 %) in arm A and in arm B respectively. One cardiac toxicity was observed (arm A).

Conclusions

First line metronomic chemotherapy for HER2 negative ABC had similar clinical activity and quite better tolerability than standard schedule and could be considered a further treatment option when chemotherapy is indicated.

Over the past few decades, first-line therapy for treating advanced and metastatic HR+/HER2-breast cancer has transformed due to the introduction of adjuvant endocrine therapy with cyclin-dependent kinase 4/6 inhibitors (CDK 4/6i). However, there is an unmet need for novel classes of endocrine therapy with superior efficacy to improve treatment outcomes and overcome CDK4/6i resistance. New generation selective estrogen receptor degraders (SERDs), orally administered and with higher bioavailability, could potentially be the novel compounds to meet this emerging need. In this paper, we review accredited clinical studies on the combining effects of CDK4/6 inhibitors and oral SERDs, report efficacy of treatment data when available, and provide a framework for future research focusing on these promising agents.

Background

Online patient education materials (OPEMs) are an increasingly popular resource for women seeking information about breast cancer. The AMA recommends written patient material to be at or below a 6th grade level to meet the general public's health literacy. Metrics such as quality, understandability, and actionability also heavily influence the usability of health information, and thus should be evaluated alongside readability.

Purpose

A systematic review and meta-analysis was conducted to determine: 1) Average readability scores and reporting methodologies of breast cancer readability studies; and 2) Inclusion frequency of additional health literacy-associated metrics.

Materials and methods

A registered systematic review and meta-analysis was conducted in Ovid MEDLINE, Web of Science, Embase.com, CENTRAL via Ovid, and ClinicalTrials.gov in June 2022 in adherence with the PRISMA 2020 statement. Eligible studies performed readability analyses on English-language breast cancer-related OPEMs. Study characteristics, readability data, and reporting of non-readability health literacy metrics were extracted. Meta-analysis estimates were derived from generalized linear mixed modeling.

Results

The meta-analysis included 30 studies yielding 4462 OPEMs. Overall, average readability was 11.81 (95% CI [11.14, 12.49]), with a significant difference (p < 0.001) when grouped by OPEM categories. Commercial organizations had the highest average readability at 12.2 [11.3,13.0]; non-profit organizations had one of the lowest at 11.3 [10.6,12.0]. Readability also varied by index, with New Fog, Lexile, and FORCAST having the lowest average scores (9.4 [8.6, 10.3], 10.4 [10.0, 10.8], and 10.7 [10.2, 11.1], respectively). Only 57% of studies calculated average readability with more than two indices. Only 60% of studies assessed other OPEM metrics associated with health literacy.

Conclusion

Average readability of breast cancer OPEMs is nearly double the AMA's recommended 6th grade level. Readability and other health literacy-associated metrics are inconsistently reported in the current literature. Standardization of future readability studies, with a focus on holistic evaluation of patient materials, may aid shared decision-making and be critical to increased screening rates and breast cancer awareness.

Introduction

Atypical or B3 lesions comprise a heterogeneous group of uncertain malignant potential. B3 lesions diagnosed on core biopsy are usually recommended for diagnostic open biopsy. Identifying factors which could allow conservative management of B3 lesions would be helpful in avoiding unnecessary surgery.

The aim of this study was to identify the upgrade rate to malignancy for B3 core biopsy lesions and to compare characteristics of lesions which were malignant and benign at excision.

Method

This retrospective study used data from BreastScreen New South Wales (NSW), Australia, of women who were diagnosed with B3 lesions on needle biopsy from 2011 to 2019.

Results

During the study period, 1927 B3 lesions were included. The upgrade rate to malignancy was 26.4%. Of the malignant lesions on excision, 29.6% were invasive and 69.2% were in situ. The rates of upgrade to invasive cancer and DCIS varied substantially with the core biopsy lesion type.

Lesions with atypia on core biopsy had significantly higher upgrade rates to malignancy at 34.7% compared to 13.6% for lesions without atypia (p < 0.0001). Lesions with malignant pathology were significantly larger than those with benign pathology (difference = 5.1 mm (95% CI 2.7–7.5 mm), p < 0.001).

Conclusions

The overall upgrade rate of B3 lesions to malignancy was 26.4%. The majority of the lesions were upgraded to DCIS instead of invasive cancer. Upgrade rates varied by lesion type. Lesions with atypia had significantly higher upgrade rates to cancer compared to lesions without atypia. Malignant lesions were significantly larger than benign lesions.