Early breast cancer in women aged 35 years or younger: A large national multicenter French population-based case control-matched analysis

by Ondine Dufour, Gilles Houvenaeghel, Jean-Marc Classe, Monique Cohen, Christelle Faure, Chafika Mazouni, Marie-Pierre Chauvet, Eva Jouve, Emile Darai, Anne-Sophie Azuar, Pierre Gimbergues, Anthony Gonçalves, Alexandre de Nonneville 

The Breast: Published: February 08, 2023

Background

There is a scarcity of data exploring early breast cancer (eBC) in very young patients. We assessed shared and intrinsic prognostic factors in a large cohort of patients aged ≤35, compared to a control group aged 36 to 50.

Methods

Patients ≤50 were retrospectively identified from a multicentric cohort of 23,134 eBC patients who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses for DFS and OS were built. To assess the independent impact of age, 1 to 3 case-control analysis was performed by matching ≤35 and 36–50 years patients.

Results

Of 6481 patients, 556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger tumors, higher grade, ER-negativity, macroscopic lymph node involvement (pN + macro), lymphovascular invasion (LVI), mastectomy, and chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with worse DFS [HR 1.56, 95% CI 1.32–1.84; p < 0.001], and OS [HR 1.29, 95% CI 1.03–1.60; p = 0.025], as were high grade, large tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was maintained in the case control-matched analysis for DFS [HR 1.56, 95%CI 1.28–1.91, p < 0.001], and OS [HR 1.33, 95%CI 1.02–1.73, p = 0.032]. When only considering patients ≤35, ER, tumor size, nodal status, and LVI were independently associated with survival in this subgroup.

Conclusions

Age ≤35 is associated with less favorable presentation and more aggressive treatment strategies. Our results support the poor prognosis value of young age, which independently persisted when adjusting for other prognostic factors and treatments.

 

Taxane rechallenge during metastatic disease in HER-2 negative breast cancer patients: Clinical activity, tolerance and survival results

by Manon Réda, Anaïs Fouquier, Isabelle Desmoulins, Didier Mayeur, Courèche Kaderbhai, Silvia Ilie, Audrey Hennequin, Bruno Coudert, Aurélie Bertaut, Sylvain Ladoire 

The Breast: Published:February 04, 2023

Background

Taxanes are major drugs for metastatic breast cancer (MBC) treatment, and are generally well tolerated, making them attractive for therapeutic reintroduction (rechallenge) during metastatic course. In view of the paucity of current literature, we questioned the usefulness of taxane rechallenge in a population of patients previously treated with taxanes in a metastatic setting.

 

Methods

From the local database of a French cancer center, we retrospectively identified 756 patients diagnosed with ER+/HER2-, or triple negative MBC, and treated between 2008 and 2021. Among them, 58 patients (7.8%) were rechallenged with taxanes. Clinical characteristics, response rates, and survival were retrospectively evaluated and compared to patients who received taxanes only once.

 

Results

Compared to non-rechallenged population, patients treated with taxane rechallenge were significantly younger, with better general status, and received more treatment. First taxane exposure led to better tumor response and was more frequently discontinued for reasons other than progression, compared to the non-rechallenged population. Taxane rechallenge led to an objective response rate of 27.6%, and a clinical benefit rate of 46.6%, with a median progression-free survival (PFS) of 5.7 months, and a median overall survival (OS) of 11.6 months. We also found a PFS2/PFS1 ratio >1.3 in 55.2% of the rechallenge population.

 

Conclusion

Although only a minority of MBC patients are concerned, taxane rechallenge appears to be a pragmatic option with an acceptable tolerance, and good efficacy, especially when these drugs have shown clinical activity earlier in the disease course, and/or have been stopped for reasons other than progression.

 

 

Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial

by Eve Rodler, Priyanka Sharma, William E Barlow, Julie R Gralow, Shannon L Puhalla, Carey K Anders, Lori Goldstein, Debu Tripathy, Ursa A Brown-Glaberman, Thu-Tam Huynh, Christopher S Szyarto, Andrew K Godwin, Harsh B Pathak, Elizabeth M Swisher, Marc R Radke, Kirsten M Timms, Danika L Lew, Jieling Miao, Lajos Pusztai, Daniel F Hayes, Gabriel N Hortobagyi 

The Lancet Oncology: VOLUME 24, ISSUE 2, P162-174, FEBRUARY 2023

Background

Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in germline BRCA1 or BRCA2 (BRCA1/2) mutation-associated metastatic breast cancer. However, studies evaluating PARP inhibitors plus platinum-based chemotherapy in germline BRCA1/2-wildtype triple-negative breast cancer are scarce. A large proportion of germline BRCA1/2-wildtype triple-negative breast cancer shows homologous recombination deficiency (HRD), resulting in a BRCA-like phenotype that might render sensitivity to PARP inhibitors. The S1416 trial assessed the efficacy of cisplatin combined with the PARP inhibitor veliparib in three predefined groups of metastatic breast cancer: germline BRCA1/2-mutated, BRCA-like, and non-BRCA-like.

 

Methods

S1416 was a randomised, double-blind, placebo-controlled, phase 2 trial conducted at 154 community and academic clinical sites across the USA. Eligible patients aged 18 years or older had metastatic or recurrent triple-negative breast cancer or germline BRCA1/2-associated metastatic or recurrent breast cancer, an Eastern Cooperative Oncology Group performance status of 0–2, and had received up to one line of chemotherapy for metastatic disease. Patients were randomly assigned (1:1) via the National Clinical Trials Network open interactive system with dynamic balancing on number of previous cytotoxic regimens for metastatic disease to receive intravenous cisplatin (75 mg/m2, day 1) combined with either veliparib or matching placebo (300 mg orally twice a day, days 1–14) on a 21-day cycle. Investigators, patients, and the sponsors were masked to treatment assignment; the study statisticians were unmasked. Central testing after ran domisation classified patients as having mutated or wildtype germline BRCA1/2. A biomarker panel established a priori was used to classify patients with wildtype germline BRCA1/2 into BRCA-like and non-BRCA-like phenotype groups, with BRCA-like status based on at least one of the biomarkers: genomic instability score (≥42), somatic BRCA1/2 mutations, BRCA1 promoter methylation, or non-BRCA1/2 homologous recombination repair germline mutations. The primary endpoint was investigator-assessed progression-free survival, analysed separately for the three predefined biomarker groups with a prespecified α value for each analysis. Efficacy analyses were done by intention to treat and included all eligible patients. Safety analyses of toxicities attributed to treatment included all patients who received at least one dose of veliparib or placebo. The study is ongoing and registered with ClinicalTrials.gov, NCT02595905.

 

Findings

Between July 7, 2016, and June 15, 2019, 335 patients were enrolled and randomly assigned. 320 patients (n=162 to cisplatin plus veliparib, all women; and n=158 to cisplatin plus placebo, 157 women and one man) were eligible for efficacy evaluation. 247 patients were classified into the three biomarker groups: germline BRCA1/2-mutated (n=37), BRCA-like (n=101), and non-BRCA-like (n=109). 73 patients could not be classified due to missing biomarker information. Median follow-up was 11·1 months (IQR 5·6–20·8). In the germline BRCA1/2-mutated group, median progression-free survival was 6·2 months (95% CI 2·3–9·2) in the cisplatin plus veliparib group and 6·4 months (4·3–8·2) in the cisplatin plus placebo group (HR 0·79 [95% CI 0·38–1·67]; log-rank p=0·54). In the BRCA-like group, median progression-free survival was 5·9 months (95% CI 4·3–7·8) in the cisplatin plus veliparib group versus 4·2 months (2·3–5·0) in the cisplatin plus placebo group (HR 0·57 [95% CI 0·37–0·88]; p=0·010). In the non-BRCA-like group, median progression-free survival was 4·0 months (95% CI 2·5–4·7) in the cisplatin plus veliparib group versus 3·0 months (2·2–4·4) in the cisplatin plus placebo group (HR 0·89 [95% CI 0·60–1·33]; p=0·57). The most common grade 3 or worse adverse events attributed to treatment were neutropenia (71 [46%] of 155 patients in the cisplatin plus veliparib group vs 29 [20%] of 147 in the cisplatin plus placebo group), leukopenia (42 [27%] vs 11 [7%]), anaemia (35 [23%] vs 12 [8%]), and thrombocytopenia (29 [19%] vs four [3%]). Serious adverse events attributed to treatment occurred in 48 (31%) patients in the cisplatin plus veliparib group and 53 (36%) patients in the cisplatin plus placebo group. Treatment-related adverse events led to death in one patient in the cisplatin plus veliparib group (sepsis) and one patient in the cisplatin plus placebo group (acute kidney injury due to cisplatin plus heart failure from previous doxorubicin exposure).

Interpretation

The addition of veliparib to cisplatin significantly improved progression-free survival in patients with BRCA-like metastatic triple-negative breast cancer, but not in patients with non-BRCA-like metastatic breast cancer. PARP inhibitors combined with platinum-based chemotherapy should be explored further in BRCA-like triple-negative breast cancer.

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.

 

 

Breast Surgery Bulletin: December 2022

 Systemic treatment with or without ablative therapies in oligometastatic breast cancer: A single institution analysis of patient outcomes

by Gauthier Glemarec, Jean Louis Lacaze, Bastien Cabarrou, Richard Aziza, Eva Jouve, Slimane Zerdoud, Eleonora De Maio, Carole Massabeau, Maxime Loo, Vincent Esteyrie, Mony Ung, Florence Dalenc, Francoise Izar, Ciprian Chira 

The Breast: Published: December 29, 2022

Purpose

Local ablative treatment (LAT) is increasingly combined with systemic therapy in oligometastatic breast cancer (OMBC), without a high-level evidence to support this strategy. We evaluated the addition of LAT to systemic treatment in terms of progression-free survival (PFS) and overall survival (OS). Secondary endpoints were local control (LC) and toxicity. We sought to identify prognostic factors associated with longer OS and PFS.

 

Methods and materials

We identified consecutive patients treated between 2014 and 2018 for synchronous or metachronous OMBC (defined as ≤ 5 metastases). LAT included stereotactic body (SBRT) and volumetric modulated arc therapy (VMAT), surgery, cryotherapy and percutaneous radiofrequency ablation (PRA). PFS and OS were calculated and Cox regression models analyzed for potential predictors of survival.

 

Results

One hundred two patients were included (no-LAT, n = 62; LAT, n = 40). Sixty-four metastases received LAT. Median follow-up was 50.4 months (95% CI [44.4; 53.4]). One patient experienced grade 3 toxicity in the LAT group. Five-year PFS and OS were 34.75% (95% CI [24.42–45.26]) and 63.21% (95% CI [50.69–73.37]) respectively. Patients receiving both LAT and systemic therapy had longer PFS and OS than those with no-LAT ([HR 0.39, p = 0.002]) and ([HR 0.31, p = 0.01]). The use of LAT, HER2-positive status and hormone-receptor positivity were associated with longer PFS and OS whereas liver metastases led to worse PFS.

 

Conclusions

LAT was associated with improved outcomes in OMBC when added to systemic treatment alone, without significantly increasing toxicity. The prognostic factors identified to extend PFS and OS may help guide clinicians in selecting patients for LAT.

 

 

Hyperbaric oxygen therapy for local late radiation toxicity in breast cancer patients: A systematic review

 

by E.L. Meier, D.R. Mink van der Molen, C.A. Lansdorp, M.C.T. Batenburg, F. van der Leij, H.M. Verkooijen, O. Boonstra, S. Hummelink, D.J.O. Ulrich 

 

The Breast: Published: December 22, 2022

 

Purpose

This systematic review aims to provide an overview of the literature on the effect of hyperbaric oxygen therapy (HBOT) on symptoms of local late radiation toxicity (LRT) in patients treated for breast cancer.

Methods

A systematic search was performed in September 2021. All studies with a sample size of ≥10 patients reporting the effect of HBOT for symptoms of LRT after radiotherapy of the breast and/or chest wall were included. The ROBINS-I tool was used for critical appraisal of methodological quality. The toxicity outcomes pain, fibrosis, lymphedema, necrosis/skin problems, arm and shoulder mobility, and breast and arm symptoms were evaluated.

Results

Nine studies concerning a total of 1308 patients were included in this review. Except for one study, sample sizes were small. Most studies had inadequate methodology with a substantial risk of bias. Post-HBOT, a significant reduction of pain was observed in 4/5 studies, of fibrosis in 1/2 studies, and of lymphedema of the breast and/or arm in 4/7 studies. Skin problems of the breast were significantly reduced in 1/2 studies, arm- and shoulder mobility significantly improved in 2/2 studies, and breast- and arm symptoms were significantly reduced in one study.

Conclusion

This systematic review indicates that HBOT might be useful for reducing symptoms of LRT in breast cancer patients, however evidence is limited. A randomized controlled trial in a larger cohort of patients including a combination of patient- and clinician-reported outcome measures would be valuable to assess the effect of HBOT on symptoms of LRT.

 

 

 

 

Adjuvant chemotherapy for resected triple negative breast cancer patients: A network meta-analysis

by Fausto Petrelli, Valentina Bertaglia, Maria Chiara Parati, Karen Borgonovo, Pushpamali De Silva, Andrea Luciani, Silvia Novello, Mario Scartozzi, Leisha A. Emens, Cinzia Solinas 

The Breast: Published: December 15, 2022

Abstract:

The current standard of care for resected early-stage triple negative breast cancer (TNBC) patients who did not receive systemic preoperative therapy is adjuvant anthracycline- and taxane-based chemotherapy (CT). A network meta-analysis (NMA) of randomized controlled trials (phase III) enrolling patients with resected stage I-III TNBC comparing adjuvant regimens was performed. Overall survival (OS) and disease-free survival (DFS) data were extracted. A total of 27 phase III clinical trials were selected including 15,242 TNBC patients. This NMA showed an OS benefit from the incorporation of capecitabine into classic anthracycline/taxane-based combinations compared to anthracyclines with or without taxanes alone.

Highlights:

·         The current adjuvant therapy for resected early-stage triple negative breast cancer is adjuvant chemotherapy.

·         A network meta-analysis (NMA) of randomized controlled trials was performed.

·         A total of 27 phase III clinical trials were selected including 15,242 TNBC patients.

·         Anthracycline- and taxane-plus capecitabine-based CT resulted in better OS than other regimens.

·         Similarly capecitabine-based triplets and the carboplatin/paclitaxel doublet ranked the best for DFS.

 

Survival and prognostic factors in oligometastatic breast cancer

 

by Annemiek van Ommen-Nijhof, Tessa G. Steenbruggen, Laura Capel, Michel Vergouwen, Marie-Jeanne T. Vrancken Peeters, Terry G. Wiersma, Gabe S. Sonke 

 

The Breast: Published: December 14, 2022

 

Background

Guidelines for oligometastatic breast cancer (OMBC) propagate multimodality treatment including polychemotherapy and local ablative treatment (LAT) of all lesions. The aim of this approach is prolonged disease remission, or even cure. Long-term outcomes in OMBC and factors associated with prognosis are largely unknown, due to the rarity of this condition. We report overall survival (OS), event-free survival (EFS), and prognostic factors in a large real-world cohort of patients with OMBC.

Methods

Patients with breast cancer and 1–3 distant metastatic lesions, treated in the Netherlands Cancer Institute between 1997 and 2020, were identified via text mining of medical files. We collected patient, tumor and treatment characteristics. The Kaplan-Meier method was used to calculate OS and EFS estimates, and Cox regression analyses to assess prognostic factors.

Results

The cohort included 239 patients, of whom 54% had ERpos/HER2neg, 20% HER2pos and 20% triple negative disease. Median follow-up was 88.0 months (95% confidence interval (CI) 82.9–93.1) during which 107 patients died and 139 developed disease progression/recurrence; median OS was 93.0 months (95%CI 66.2–119.8). Factors associated with OS in multivariable analysis were subtype, disease-free interval and radiologic response to first-line systemic therapy; LAT was associated with EFS, but not OS.

Conclusions

In this large real-world cohort of patients with OMBC, OS and EFS compare favorably to survival in the general MBC population. Radiologic complete response to first-line systemic therapy was associated with favorable OS and EFS, indicating the importance of early optimal systemic therapy. The value of LAT in OMBC requires further study.

 

Comparison of clinicopathological characteristics and response to neoadjuvant chemotherapy between HER2-low and HER2-zero breast cancer

 

by Shuling Zhou, Ting Liu, Xiaying Kuang, Tiantian Zhen, Huijuan Shi, Ying Lin, Nan Shao 

 

The Breast: Published: December 13, 2022

 

Novel anti-HER2 antibody-drug conjugates trastuzumab deruxtecan (DS-8201a) showed its effect in previously-treated HER2-low metastatic breast cancer, suggesting a promising future in HER2-low breast cancer. We retrospectively reviewed the clinicopathological data of 325 patients with stage I–III HER2 negative breast cancer who received neoadjuvant chemotherapy in the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2021. In general, 91 patients (28.0%) were HER2-zero, and 234 patients (72.0%) were HER2-low. The pathological complete response (pCR) rate of the entire cohort was 17.3%. The pCR rate was 16.7% in HER2-low group, and 18.9% in HER2-zero group, showing no significant difference. Patients with HER2-low tumors had significantly longer overall survival (OS) than patients with HER2-zero tumors. ER status was the affecting factor of OS in HER2-low patients in both univariate and multivariate analysis. In conclusion, evidence for HER2-low BC as a distinct entity is insufficient, and more efforts are needed to standardize the scoring of HER2-low breast cancer.

Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer

 

by Arlene Chan, Manuel Ruiz-Borrego, Gavin Marx, A. Jo Chien, Hope S. Rugo, Adam Brufsky, Michael Thirlwell, Maureen Trudeau, Ron Bose, José A. García-Sáenz, Daniel Egle, Barbara Pistilli, Johanna Wassermann, Kerry A. Cheong, Benjamin Schnappauf, Dieter Semsek, Christian F. Singer, Navid Foruzan, Daniel DiPrimeo, Leanne McCulloch, Sara A. Hurvitz, Carlos H. Barcenas 

 

The Breast: Published: December 13, 2022

 

Background

Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies.

Methods

Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L.

Results

563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed.

Conclusions

These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective.

 

 

Does mainstream BRCA testing affect surgical decision-making in newly-diagnosed breast cancer patients?

 

by Quratul Ain, Caroline Richardson, Miriam Mutebi, Angela George, Zoe Kemp, Jennifer E. Rusby 

 

 

The Breast: Published: December 06, 2022

 

Background

Germline pathogenic variants mutations) in the BRCA1 and BRCA2 genes cause an increased risk of breast cancer and ovarian cancer. Mainstream cancer genetic testing (MCG) was introduced for breast cancer patients in our unit in 2013. Non-geneticist clinicians have been trained to offer genetic testing during initial treatment planning. We assessed the impact of timely test results on surgical decision-making.

Methods

Women who had undergone mainstream genetic testing for breast cancer between September 2013 and September 2018 were identified from a prospective database. Surgical data were collected retrospectively.

Results

580 eligible women had mainstream genetic testing. For 474 this was their first breast cancer diagnosis. The median age was 46 years (interquartile range (IQR) 38–57). The indications were: age ≤45 years for 233 (49%); triple negative disease for 192 women (40.5%); bilateral breast cancer age <60 for 39 (8%) and other for 72 (14%) women. The median time for test initiation to result was 18 days (IQR 15-21). 302 (64% received results before surgery. 88% of those found to have a BRCA mutation before surgery opted for bilateral mastectomy (compared to 5% with BRCA wild type). An additional 106 patients had a new diagnosis on a background of previous treatment. Of these all with a pathogenic variant chose bilateral mastectomy.

Conclusion

Timely BRCA gene testing influences surgeons’ and patients’ choice of surgery. It reassures women with a negative result and allows those with a positive result to take an active decision about the management of their future risk.