Breast Surgery Bulletin: Feb 2023

 

Factors associated with weight gain after breast cancer: Results from a community-based survey of Australian women

 

by Carolyn Ee, Adele Cave, Vaishnavi Vaddiparthi, Dhevaksha Naidoo, John Boyages 

 

The Breast: Published: January 25, 2023

 

Purpose

Weight gain after breast cancer is common. The aim of this study was to determine factors associated with weight gain after breast cancer in Australian women.

Methods

A cross-sectional online survey was conducted between November 2017 and January 2018. Women living in Australia who self-identified as having breast cancer or ductal carcinoma in-situ were eligible. We created stepwise linear and logistic regression models to evaluate predictors for absolute and clinically significant (≥5%) weight gain respectively.

Results

Data from 276 women were analysed. Most were Caucasian and 92% had been diagnosed with Stage 0-III breast cancer. Absolute weight gain was associated with hot flushes, being in the menopausal transition at diagnosis, being less physically active than at diagnosis, lower eating self-efficacy when watching television or using a computer, and higher self-efficacy when anxious or nervous (F-ratio = 3.26, R2-adjusted = 0.16, p < .001). Clinically significant weight gain was associated with tamoxifen use (OR 2.7), being less physically active than at diagnosis (OR 3.1), and lower eating self-efficacy when watching television or using a computer (OR 0.82) (Chi-square 64.94, df = 16, p < .001). Weight gain was not associated with chemotherapy, radiotherapy, aromatase inhibitor use, number of lymph nodes removed, or body mass index at diagnosis.

Conclusions

Interventions to prevent weight gain after breast cancer, particularly aiming to maintain physical activity, should be targeted at women receiving tamoxifen. The role of eating self-efficacy, especially attentive eating, in managing weight after breast cancer should be explored.

 

Axillary lymph node dissection: Dead or still alive?

 

by Anna C. Beck, Monica Morrow 

 

The Breast: Published: January 23, 2023

 

Highlights

·         Axillary surgery in BC has been de-escalated for a significant group of patients, but an ALND is still necessary for some

·         ALND remains necessary for staging in patients where SLNB has not been demonstrated to be accurate

·         This includes patients with clinically palpable lymph nodes and patients with cT4 or cN2-3 disease

·         ALND is required for local control in patients with a heavy axillary tumor burden and recurrent axillary disease

·         Use of newer systemic therapy may require complete axillary staging with ALND to determine eligibility for use.

Abstract

Although sentinel lymph node biopsy is now the primary method of axillary staging and is therapeutic for patients with limited nodal disease, axillary lymph node dissection (ALND) is still necessary for staging in groups where sentinel lymph node biopsy has not been proven to be accurate and to maintain local control in those with a heavy axillary tumor burden. Additionally, newer approaches to systemic therapy tailored to risk level sometimes necessitate knowledge of the number of involved axillary nodes which can only be obtained with ALND. Ongoing trials will address whether there are additional circumstances where radiotherapy can replace ALND.

 

The underused potential of breast conserving therapy after neoadjuvant system treatment – Causes and solutions

 

by André Pfob, Peter Dubsky 

 

The Breast: Published: January 17, 2023

 

Abstract

Breast conserving therapy (BCT), consisting of breast conserving surgery and subsequent radiotherapy, is an equivalent option to mastectomy for women with early breast cancer. Although BCT after neoadjuvant systemic treatment (NAST) has been routinely recommend by international guidelines since many years, the rate of BCT worldwide varies largely and its potential is still underused. While the rate of BCT in western countries has increased over the past decades to currently about 70%, the rate of BCT is as low as 10% in other countries. In this review, we will evaluate the underused potential of breast conservation after NAST, identify causes, and discuss possible solutions. We identified clinical and non-clinical causes for the underuse of BCT after NAST including uncertainties within the community regarding oncologic outcomes, the correct tumor localization after NAST, the management of multifocal and multicentric tumors, margin assessment, disparities of socio-economic aspects on a patient and national level, and psychological biases affecting the shared decision-making process between patients and clinicians. Possible solutions to mitigate the underuse of BCT after NAST include interdisciplinary teams that keep the whole patient pathway in mind, optimized treatment counseling and shared decision-making, and targeted financial support to alleviate disparities.

 

Trastuzumab emtansine vs lapatinib and capecitabine in HER2-positive metastatic breast cancer brain metastases: A real-world study

by Thibaut Sanglier, Jinjoo Shim, Neil Lamarre, Claudia Peña-Murillo, Vincent Antao, Filippo Montemurro 

The Breast: Published: January 15, 2023

Background

Trastuzumab emtansine (T-DM1) has demonstrated improvements in survival and neurological symptoms in patients with breast cancer with brain metastases (BCBM). This real-world study investigated the effectiveness of T-DM1 versus lapatinib plus capecitabine (LC) in patients with BCBM.

Methods

This retrospective, observational study evaluated patients with HER2–positive BCBM using a real-world database. Eligible patients had initiated T-DM1 or LC with a prior diagnosis of brain metastasis and ≥1 prior metastatic breast cancer treatment. The primary endpoint was overall survival (OS); secondary endpoints were time to next relevant treatment or death (TTNT) and real-world progression-free survival (rwPFS). An inverse probability of treatment weighting (IPTW) approach was used to account for differences in potential baseline characteristics between treatment groups. Outcomes were described using the Kaplan-Meier method, and the average treatment effect of initiating T-DM1 versus LC was estimated using weighted Cox proportional hazard models and hazard ratio (HR).

Results

A total of 214 patients were available for analysis (T-DM1, n = 161; LC, n = 53). Demographics and baseline characteristics were generally well-balanced between treatment groups after weighting. After weighting, median OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34–0.89]; P=0.013). Median TTNT was 9.0 (T-DM1) versus 6.0 (LC) months (HR, 0.55 [95% CI, 0.36–0.85]; P = 0.005). After weighting, median rwPFS was 6.0 (T-DM1) versus 4.0 (LC) months (HR, 0.50 [95% CI, 0.36–0.69]; P < 0.001).

Conclusions

These results support the superior effectiveness and clinical relevance of T-DM1 versus LC in patients with HER2-positive BCBM in the real world.

 

How I treat HER2-low advanced breast cancer

 

by Ilana Schlam, Sara M. Tolaney, Paolo Tarantino 

 

The Breast: Published: January 11, 2023

 

Introduction

Targeting low levels of human receptor epidermal growth factor 2 (HER2) expression has reshaped the treatment paradigm for half of the patients with advanced breast cancer. HER2-low is currently defined as a HER2 immunohistochemical expression of 1+ or 2+ without amplification by in-situ hybridization. Until recently, HER2-targeted agents were ineffective in treating patients with HER2-low disease.

Areas covered

In this narrative review, we summarize the current management of HER2-low breast cancer. We highlight the findings of the DESTINY-Breast 04 phase 3 trial, which confirmed the efficacy of trastuzumab-deruxtecan (T-DXd) for the treatment of patients with advanced, pretreated HER2-low breast cancer. We also discuss how to implement this new treatment option in treatment algorithms of hormone receptor (HR)-positive and triple-negative tumors, as well as how to optimally manage selected toxicities of T-DXd.

Expert opinion

T-DXd is currently the standard of care for patients with advanced, pretreated, HER2-low breast cancer. Based on the design of the DESTINY-Breast04 trial, the current optimal place in treatment algorithms is after the first line of chemotherapy, both in HR-positive and triple-negative breast cancer. Up to 10–15% of the patients receiving T-DXd are expected to develop interstitial lung disease, which in 1–2% of the cases can be fatal. Adequate monitoring and prompt management are required to minimize the impact of ILD and to safely implement T-DXd in clinical practice.

 

Polygenic risk scores and breast cancer risk prediction

 

by Eleanor Roberts, Sacha Howell, Gareth Evans 

 

The Breast: VOLUME 67, P71-77, FEBRUARY 2023

 

Abstract

Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have the potential to improve screening and prevention strategies. PRS combine the risk from Single nucleotide polymorphisms (SNPs) associated with breast cancer in Genome Wide Association Studies (GWAS) and explain over 30% of breast cancer heritability. When incorporated into risk models, the more personalised risk assessment derived from PRS, help identify women at higher risk of breast cancer development and enables the implementation of stratified screening and prevention approaches. This review describes the role of PRS in breast cancer risk prediction including the development of PRS and their clinical application. We have also examined the role of PRS within more well-established risk prediction models which incorporate known classic risk factors and discuss the interaction of PRS with these factors and their capacity to predict breast cancer subtypes. Before PRS can be implemented on a population-wide scale, there are several challenges that must be addressed. Perhaps the most pressing of these is the use of PRS in women of non-White European origin, where PRS have been shown to have attenuated risk prediction both in discrimination and calibration. We discuss progress in developing and applying PRS in non-white European populations. PRS represent a significant advance in breast cancer risk prediction and their further development will undoubtedly enhance personalisation.

 

Omission of axillary sentinel lymph node biopsy in early invasive breast cancer

 

by Toralf Reimer 

 

The Breast: Published: January 09, 2023

 

Abstract

 Local treatment of the axilla in clinically node-negative (cN0) early breast cancer patients with routine sentinel lymph node biopsy (SLNB) is debated after publication of ACOSOG Z0011 data in 2010. Currently, prospective randomized surgical trials investigating the omission of SLNB in upfront breast-conserving surgery (BCS) and in the neoadjuvant setting, respectively. Several prospective randomized trials (SOUND, INSEMA, BOOG 2013–08, and NAUTILUS) with axillary observation alone versus SLNB in cN0 patients and primary BCS have primary objectives to evaluate oncologic safety when omitting SLNB. The Italian SOUND trial was the earliest to open in 2012 and has completed accrual in 2017. First oncologic outcome data are expected soon for SOUND and at the end of 2024 for INSEMA. Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to de-escalate surgery in patients who have a pCR. Two prospective single-arm trials (EUBREAST-01, ASICS) include only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) and type of surgery will be defined according to the response to NAST rather than on the classical T and N status. The ongoing trials will hopefully help us to understand whether we might take the best therapeutic decisions without the pathologic evaluation of nodal status.

 

A systematic review of the impact of the COVID-19 pandemic on breast cancer screening and diagnosis

 

by Tong Li, Brooke Nickel, Preston Ngo, Kathleen McFadden, Meagan Brennan, M Luke Marinovich, Nehmat Houssami 

 

The Breast: VOLUME 67, P78-88, FEBRUARY 2023

Background

Breast cancer care has been affected by the COVID-19 pandemic. This systematic review aims to describe the observed pandemic-related changes in clinical and health services outcomes for breast screening and diagnosis.

Methods

Seven databases (January 2020–March 2021) were searched to identify studies of breast cancer screening or diagnosis that reported observed outcomes before and related to the pandemic. Findings were presented using a descriptive and narrative approach.

Results

Seventy-four studies were included in this systematic review; all compared periods before and after (or fluctuations during) the pandemic. None were assessed as being at low risk of bias. A reduction in screening volumes during the pandemic was found with over half of studies reporting reductions of ≥49%. A majority (66%) of studies reported reductions of ≥25% in the number of breast cancer diagnoses, and there was a higher proportion of symptomatic than screen-detected cancers. The distribution of cancer stage at diagnosis during the pandemic showed lower proportions of early-stage (stage 0–1/I-II, or Tis and T1) and higher proportions of relatively more advanced cases than that in the pre-pandemic period, however population rates were generally not reported.

Conclusions

Evidence of substantial reductions in screening volume and number of diagnosed breast cancers, and higher proportions of advanced stage cancer at diagnosis were found during the pandemic. However, these findings reflect short term outcomes, and higher-quality research examining the long-term impact of the pandemic is needed.

 

[Clinical Picture] Chest mass in a transgender man after top surgery

 

by Chandler S Cortina, Amanda L Kong 

 

The Lancet Oncology CLINICAL PICTURE| VOLUME 24, ISSUE 1, E57, JANUARY 2023

 

A 37-year-old transgender man presented to the outpatient Breast Care Clinic at the Medical College of Wisconsin (WI, USA) for evaluation of a new left chest mass in April, 2022, which he had noticed 1 month earlier. The mass was painless, and he had no other symptoms. His previous surgical history was notable in that he had undergone chest masculinisation surgery, colloquially called top surgery, 5 years earlier and was on gender-affirming testosterone therapy for the past 10 years. His family history was significant for a mother who had passed away from breast cancer in her 20s and a sister who was recently diagnosed with breast cancer at age 39 years.

 

Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial

 

by Stephen R D Johnston, Masakazu Toi, Joyce O'Shaughnessy, Priya Rastogi, Mario Campone, Patrick Neven, Chiun-Sheng Huang, Jens Huober, Georgina Garnica Jaliffe, Irfan Cicin, Sara M Tolaney, Matthew P Goetz, Hope S Rugo, Elzbieta Senkus, Laura Testa, Lucia Del Mastro, Chikako Shimizu, Ran Wei, Ashwin Shahir, Maria Munoz, Belen San Antonio, Valérie André, Nadia Harbeck, Miguel Martin, monarchE Committee Members 

 

The Lancet Oncology: VOLUME 24, ISSUE 1, P77-90, JANUARY 2023

 

Background

Adjuvant abemaciclib plus endocrine therapy previously showed a significant improvement in invasive disease-free survival and distant relapse-free survival in hormone receptor-positive, human epidermal growth factor receptor 2 (HER2; also known as ERBB2)-negative, node-positive, high-risk, early breast cancer. Here, we report updated results from an interim analysis to assess overall survival as well as invasive disease-free survival and distant relapse-free survival with additional follow-up.

Methods

In monarchE, an open-label, randomised, phase 3 trial, adult patients (aged ≥18 years) who had hormone receptor-positive, HER2-negative, node-positive, early breast cancer at a high risk of recurrence with an Eastern Cooperative Oncology Group performance status of 0 or 1 were recruited from 603 sites including hospitals and academic and community centres in 38 countries. Patients were randomly assigned (1:1) by means of an interactive web-based response system (block size of 4), stratified by previous chemotherapy, menopausal status, and region, to receive standard-of-care endocrine therapy of physician's choice for up to 10 years with or without abemaciclib 150 mg orally twice a day for 2 years (treatment period). All therapies were administered in an open-label manner without masking. High-risk disease was defined as either four or more positive axillary lymph nodes, or between one and three positive axillary lymph nodes and either grade 3 disease or tumour size of 5 cm or larger (cohort 1). A smaller group of patients were enrolled with between one and three positive axillary lymph nodes and Ki-67 of at least 20% as an additional risk feature (cohort 2). This was a prespecified overall survival interim analysis planned to occur 2 years after the primary outcome analysis for invasive disease-free survival. Efficacy was assessed in the intention-to-treat population. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03155997, and is ongoing.

Findings

Between July 17, 2017, and Aug 12, 2019, 5637 patients were randomly assigned (5601 [99·4%] were women and 36 [0·6%] were men). 2808 were assigned to receive abemaciclib plus endocrine therapy and 2829 were assigned to receive endocrine therapy alone. At a median follow-up of 42 months (IQR 37–47), median invasive disease-free survival was not reached in either group and the invasive disease-free survival benefit previously reported was sustained: HR 0·664 (95% CI 0·578–0·762, nominal p<0·0001). At 4 years, the absolute difference in invasive disease-free survival between the groups was 6·4% (85·8% [95% CI 84·2–87·3] in the abemaciclib plus endocrine therapy group vs 79·4% [77·5–81·1] in the endocrine therapy alone group). 157 (5·6%) of 2808 patients in the abemaciclib plus endocrine therapy group died compared with 173 (6·1%) of 2829 patients in the endocrine therapy alone group (HR 0·929, 95% CI 0·748–1·153; p=0·50). The most common grade 3–4 adverse events were neutropenia (in 548 [19·6%] of 2791 patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of 2800 patients in the endocrine therapy alone group), leukopenia (318 [11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six [0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800 receiving endocrine therapy. There were two treatment-related deaths in the abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none in the endocrine therapy alone group.

Interpretation

Adjuvant abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the completion of treatment with an absolute increase at 4 years, further supporting the use of abemaciclib in patients with high-risk hormone receptor-positive, HER2-negative early breast cancer. Further follow-up is needed to establish whether overall survival can be improved with abemaciclib plus endocrine therapy in these patients.