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.