Revision Breast Reconstruction with Prepectoral Pocket Conversion of Submuscular Breast Implants

 

Revision Breast Reconstruction with Prepectoral Pocket Conversion of Submuscular Breast Implants

 

by Kraenzlin, Franca; Chopra, Karan; Kokosis, George; Venturi, Mark L.; Mesbahi, Ali; Nahabedian, Maurice Y.

 

Plastic and Reconstructive Surgery: May 2021 - Volume 147 - Issue 5 - p 743e-748e

 

Background:

Prepectoral reconstruction using prosthetic devices has demonstrated a notable increase in popularity and confers a number of advantages over subpectoral placement, including minimal animation, no pain secondary to muscle spasm, and less device displacement or malposition. As such, more women with implants in the dual-plane position are seeking a remedy for animation deformities, chronic pain caused by muscle spasm, and implant malposition. The purpose of this study was to review outcomes following the conversion from subpectoral to prepectoral implant placement.

 Methods:

This was a retrospective review of 63 patients who underwent breast implant conversion from the subpectoral plane to the prepectoral plane from 2009 to 2019.

Results:

 A total of 73 implant pocket conversions from subpectoral to prepectoral were performed on 41 women who met inclusion criteria for this study. The mean time interval from the initial subpectoral operation to the prepectoral conversion was 1608.4 days. The reasons cited for prepectoral conversion was animation deformity (87.8 percent), significant levels of pain related to the implant (34.1 percent), capsular contracture (26.8 percent), or asymmetries and implant displacements (9.8 percent); 7.8 percent of individuals continued to experience their presenting symptom after plane conversion. Rippling and wrinkling were noted in 19.5 percent of individuals and edge visibility was documented in 4.9 percent. Complication rates were low, and no patients experienced necrosis of the mastectomy flap or nipple-areola complex.

Conclusions:

The use of prepectoral conversion for revision implant-based breast reconstruction successfully resolves animation deformity. This technique can be reliably and safely performed in a variety of patient demographics. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Management of Symptomatic Patients with Textured Implants

 

Management of Symptomatic Patients with Textured Implants

 

by Asaad, Malke; Offodile, Anaeze C.; Santanelli Di Pompeo, Fabio; Bevers, Therese B.; Stelly, Sharon; Carew, Lori A.; Barnea, Yoav; Miranda, Roberto N.; Butler, Charles E.; Clemens, Mark W.

 

Plastic and Reconstructive Surgery: May 2021 - Volume 147 - Issue 5S - p 58S-68S

 

Summary:

 Proper management of symptomatic textured implant patients is critical to identify and treat associated oncologic disease. Textured surface breast implants were first introduced more than 50 years ago in an effort to decrease high rates of capsular contracture and implant malposition observed with first-generation smooth surface breast implants. Textured implants were dominant over smooth devices in the United States in the late 1990s, but they fell out of favor for newer-generation smooth implants, while texture remained the dominant selling implants worldwide until recently. A class I device recall by the US Food and Drug Administration in 2019 precipitated a removal of the highest selling implant worldwide, Allergan Biocell, due to a disproportionately increased risk of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL). Operative strategies, such as bacterial control at the time of textured implant insertion, have not been credibly shown to affect or prevent the future development of BIA-ALCL. BIA-ALCL patients require complete surgical excision of their disease, whereas textured implant patients who are otherwise asymptomatic do not require surgical removal. For suspicious cases, diagnostic testing with CD30 immunohistochemistry should be performed before any surgical intervention. Capsules are evaluated with 12 strategic regional biopsies in a standardized approach. If surgeons are revising or exchanging textured implants, they may reasonably consider a total capsulectomy, though this is not advocated by the Food and Drug Administration or national societies, and has not been shown to mitigate future risk of BIA-ALCL. The purpose of this article is to review data on and outcomes for textured surface implants, disease-associated risk, and the management strategy for revisionary surgery and device surveillance.

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

 

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

by Benjamin Daniels, Belinda E. Kiely, Monica Tang, Nehmat Houssami, Sarah J. Lord, Sallie-Anne Pearson 

The Breast: Published: May 07, 2021

Highlights

•Real-world T-DM1 recipients are older than trial participants.

•Real-world T-DM1 recipients have more prior pertuzumab exposure than trial participants.

•Median overall survival was 10 months shorter than that reported from the trial.

Purpose

We aim to describe the treatment patterns and overall survival (OS) outcomes in patients receiving trastuzumab emtansine (T-DM1) for HER2-positive metastatic breast cancer (HER2+MBC) in routine clinical care.

Methods

Retrospective, whole-of-population cohort study of people initiating T-DM1 for HER2+MBC between October 2015 and May 2019 in Australia. We used dispensing claims to estimate time-to-T-DM1 initiation, duration of treatment, and treatments administered prior to and following T-DM1 therapy. We estimated OS from T-DM1 initiation and stratified results based on whether patients received first- or second-line T-DM1 treatment. We benchmarked outcomes to those reported in the pivotal, EMILIA trial.

Results

345 patients initiated T-DM1: 309 as second-line therapy for HER2+MBC and 36 as first-line therapy. 51% of patients had received endocrine therapy and 98% of second-line patients received pertuzumab prior to starting T-DM1. The median age was 57 years (53 in EMILIA); median time-to-T-DM1 initiation from start of HER2-targeted therapy for HER2+MBC was 11.6 months (IQR: 7.9–16.6); median duration of T-DM1 treatment was 6.5 months (3.1–13.5; 7.6 months in EMILIA), and median OS was 19.3 months (7.9–29.5; 29.9 months in EMILIA).

Conclusions

Our findings highlight differences in patient characteristics (older, more previous pertuzumab therapy) and outcomes (shorter OS) from the T-DM1 pivotal trial and provide real-world estimates that can inform patient, clinician and policy, decisions around the use of HER2-targeted therapies in routine clinical care.

Locoregional therapy in de novo metastatic breast cancer. The unanswered question

 

Locoregional therapy in de novo metastatic breast cancer. The unanswered question

by Maria-Joao Cardoso, Kefah Mokbel 

The Breast: Published: May 07, 2021

Breast cancer has now overtaken lung cancer as the world's mostly commonly-diagnosed cancer, according to statistics released by the International Agency for Research on Cancer (IARC) in December 2020. Five to eight percent of newly diagnosed breast cancer cases are metastatic at diagnosis. Intriguingly this number has not changed over the last decade even with the widespread use of more sensitive systemic staging modalities like PET-CT.

[Articles] Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial

 

[Articles] Intraoperative irradiation for early breast cancer (ELIOT): long-term recurrence and survival outcomes from a single-centre, randomised, phase 3 equivalence trial

by Roberto Orecchia, Umberto Veronesi, Patrick Maisonneuve, Viviana Enrica Galimberti, Roberta Lazzari, Paolo Veronesi, Barbara Alicja Jereczek-Fossa, Federica Cattani, Claudia Sangalli, Alberto Luini, Pietro Caldarella, Marco Venturino, Daniele Sances, Stefano Zurrida, Giuseppe Viale, Maria Cristina Leonardi, Mattia Intra 

The Lancet Oncology : VOLUME 22, ISSUE 5, P597-608, MAY 01, 2021

Background

In the randomised, phase 3 equivalence trial on electron intraoperative radiotherapy (ELIOT), accelerated partial breast irradiation (APBI) with the use of intraoperative radiotherapy was associated with a higher rate of ipsilateral breast tumour recurrence (IBTR) than whole-breast irradiation (WBI) in patients with early-stage breast cancer. Here, we aimed to examine the planned long-term recurrence and survival outcomes from the ELIOT trial.

Methods

This single-centre, randomised, phase 3 equivalence trial was done at the European Institute of Oncology (Milan, Italy). Eligible women, aged 48–75 years with a clinical diagnosis of a unicentric breast carcinoma with an ultrasound diameter not exceeding 25 mm, clinically negative axillary lymph nodes, and who were suitable for breast-conserving surgery, were randomly assigned (1:1) via a web-based system, with a random permuted block design (block size of 16) and stratified by clinical tumour size, to receive post-operative WBI with conventional fractionation (50 Gy given as 25 fractions of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial was open label and no-one was masked to treatment group assignment. The primary endpoint was the occurrence of IBTR. The trial was designed assuming a 5-year IBTR rate of 3% in the WBI group and equivalence of the two groups, if the 5-year IBTR rate in the ELIOT group did not exceed a 2·5 times excess, corresponding to 7·5%. Overall survival was the secondary endpoint. The main analysis was done by intention to treat. The cumulative incidence of IBTR events and overall survival were assessed at 5, 10, and 15 years of follow-up. This trial is registered with ClinicalTrials.gov, NCT01849133.

Findings

Between Nov 20, 2000, and Dec 27, 2007, 1305 women were enrolled and randomly assigned: 654 to the WBI group and 651 to the ELIOT group. After a median follow-up of 12·4 years (IQR 9·7–14·7), 86 (7%) patients developed IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62, 95% CI 2·68–7·95, p<0·0001). In the ELIOT group, the 5-year IBTR rate was 4·2% (95% CI 2·8–5·9), the 10-year rate was 8·1% (6·1–10·3), and the 15-year rate was 12·6% (9·8–15·9). In the WBI group, the 5-year IBTR rate was 0·5% (95% CI 0·1–1·3), the 10-year rate was 1·1% (0·5–2·2), and the 15-year rate was 2·4% (1·4–4·0). At final follow-up on March 11, 2019, 193 (15%) women had died from any cause, with no difference between the two groups (98 deaths in the ELIOT group vs 95 in the WBI group; HR 1·03, 95% CI 0·77–1·36, p=0·85). In the ELIOT group, the overall survival rate was 96·8% (95% CI 95·1–97·9) at 5 years, 90·7% (88·2–92·7) at 10 years, and 83·4% (79·7–86·4) at 15 years; and in the WBI group, the overall survival rate was 96·8% (95·1–97·9) at 5 years, 92·7% (90·4–94·4) at 10 years, and 82·4% (78·5–85·6) at 15 years. We did not collect long-term data on adverse events.

Interpretation

The long-term results of this trial confirmed the higher rate of IBTR in the ELIOT group than in the WBI group, without any differences in overall survival. ELIOT should be offered to selected patients at low-risk of IBTR.

Preoperative non-palpable breast lesion localization, innovative techniques and clinical outcomes in surgical practice: a systematic review and meta-analysis

 

Preoperative non-palpable breast lesion localization, innovative techniques and clinical outcomes in surgical practice: a systematic review and meta-analysis

 

by Francesco Garzotto, Rosanna Irene Comoretto, Silvia Michieletto, Gianpaolo Franzoso, Marcello Lo Mele, Dario Gregori, Maria Giuseppina Bonavina, Fernando Bozza, Francesca Caumo, Tania Saibene 

The Breast: VOLUME 58, P93-105, AUGUST 01, 2021

Highlights

•Positioning and localization of reflectors' is nearly of the 100% rate of success. Overall, positive margins rates were 12% (8–17%).

•The re-excision and clear margins rates were 12% (95% CI, 8–17%) and 87% (80–92%), respectively.

•Comparing NWNI and WGL techniques, positive margin rate is lower for the first one and re-excision rate is slightly higher using the latter.

•This technology overcomes the limitations related to other techniques: migrations, the coordination between radiology and surgery, the use of radioactive substances.

•The procedure is comfortable for the radiologist while allow surgeon at resecting the non-palpable lesions ensuring clear margins, avoiding the re-excisions.

•The cosmetic outcome can be obtained minimizing the resection of healthy-tissue.

Abstract

Pre-operative localization of non-palpable breast lesions with non-wired non-ionizing (NWNI) techniques may improve clinical outcomes as reoperation rate, cosmetic outcome and contribute to organizational aspects improvement in breast-conserving surgery (BCS). However only limited literature is available and clinical studies involving these forefront devices are often small and non-randomized. Furthermore, there is a lack of consensus on free margins and cosmetic outcomes definitions. The objective of the present meta-analysis was to determine the crude clinical outcomes reported for the NWNI techniques on BCS. A literature search was performed of PubMed, Embase and Scopus databases up to February 2021 in order to select all prospective or retrospective clinical trials on pre-operative breast lesion localization done with NWNI devices. All studies were assessed following the PRISMA recommendations. Continuous outcomes were described in averages corrected for sample size, while binomial outcomes were described using the weighted average proportion.

Twenty-seven studies with a total of 2103 procedures were identified. The technique is consolidated, showing for both reflectors’ positioning and localization nearly the 100% rate of success. The re-excision and clear margins rates were 14% (95% CI, 11–17%) and 87% (80–92%), respectively. Overall, positive margins rates were 12% (8–17%). In studies that compared NWNI and wire localization techniques, positive margin rate is lower for the first techniques (12%, 6–22% vs 17%, 12–23%) and re-excision rate is slightly higher using the latter (13%, 9–19% vs 16%, 13–18%).

Pre-operative NWNI techniques are effective in the localization of non-palpable breast lesions and are promising in obtaining clear (or negative) margins minimizing the need for re-excision and improving the cosmetic outcomes. Randomized trials are needed to confirm these findings.

Prediction of severe neutropenia and diarrhoea in breast cancer patients treated with abemaciclib

 

Prediction of severe neutropenia and diarrhoea in breast cancer patients treated with abemaciclib

 

by Natansh D. Modi, Ahmad Y. Abuhelwa, Sarah Badaoui, Emily Shaw, Kiran Shankaran, Ross A. McKinnon, Andrew Rowland, Michael J. Sorich, Ashley M. Hopkins

 

The Breast:  VOLUME 58, P57-62, AUGUST 01, 2021

 

Introduction

Neutropenia and diarrhoea are common and potentially serious adverse events associated with abemaciclib in advanced breast cancer (ABC), and the risk factors have been minimally explored. The study aimed to develop clinical prediction tools that allow personalized predictions of neutropenia and diarrhoea following abemaciclib initiation.

Materials and methods

Data was pooled from MONARCH 1, 2 and 3 trials investigating abemaciclib. Cox proportional hazard analysis was used to assess the association between pre-treatment clinicopathological data and grade ≥3 diarrhoea and neutropenia occurring within the first 365 days of abemaciclib use.

Results

Older age was associated with increased risk of grade ≥3 diarrhoea [HR [95%CI] for age > 70: 1.72 [1.14–2.58]; P = 0.009]. A clinical prediction tool for abemaciclib induced grade ≥3 neutropenia was optimally defined by race, ECOGPS and white blood cell count. Large discrimination between subgroups was observed; the highest risk subgroup had a 64% probability of grade ≥3 neutropenia within the first 365 days of abemaciclib (150 mg twice daily) + fulvestrant/NSAI, compared to 5% for the lowest risk subgroup.

Conclusion

The study identified advanced age as significantly associated with an increased risk of abemaciclib induced grade ≥ 3 diarrhoea. A clinical prediction tool, defined by race, ECOGPS and pre-treatment white blood cell count, was able to discriminate subgroups with significantly different risks of grade ≥3 neutropenia following abemaciclib initiation. The tool may enable improved interpretation of personalized risks and the risk-benefit ratio of abemaciclib.

Not All Breast Explants Are Equal: Contemporary Strategies in Breast Explantation Surgery

 

Not All Breast Explants Are Equal: Contemporary Strategies in Breast Explantation Surgery

 

by Tanna, Neil; Calobrace, M. Bradley; Clemens, Mark W.; Hammond, Dennis C.; Nahabedian, Maurice Y.; Rohrich, Rod J.; Zhang, Ben H.; Bregman, Dana; Perry, Adam D. 

 

Plastic and Reconstructive Surgery: April 2021 - Volume 147 - Issue 4 - p 808-818

 

Summary:

Breast implant removal and replacement has been a common secondary breast procedure in the long-term maintenance of breast augmentation, but more recently growing concerns about silicone-related systemic illness, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), and changing perceptions of aesthetic beauty have seen breast implant removal without replacement become increasingly requested by patients. Explantation can be challenging, especially when performed with a total capsulectomy. Currently, there is no evidence regarding whether a partial or total capsulectomy has any effect on BIA-ALCL risk mitigation in patients that have textured implants without disease. Total capsulectomy with incomplete resection of a mass can contribute to hyperprogression of BIA-ALCL and death. There have also been cases of BIA-ALCL diagnosed years after removal of the textured device and “total capsulectomy.” Therefore, the common practice of simple prophylactic capsulectomy in a textured implant to mitigate future disease has not been established and at the current time should be discouraged. In addition, aesthetic outcomes can be quite variable, and patients should have appropriate preoperative counseling regarding the indications and contraindications for explantation, associated risks, financial implications, and postoperative appearance. The authors review salient aspects related to the planning and management of breast implant removal.

Correlation Between Week 24 Trastuzumab-dkst Response and Week 48 Progression-Free Survival: The HERITAGE Trial

 

Correlation Between Week 24 Trastuzumab-dkst Response and Week 48 Progression-Free Survival: The HERITAGE Trial

by Hope S. Rugo, Eduardo J. Pennella, Unmesh Gopalakrishnan, Miguel Hernandez-Bronchud, Jay Herson, Hans Friedrich Koch, Subramanian Loganathan, Sarika Deodhar, Ashwani Marwah, Alexey Manikhas, Igor Bondarenko, Joseph D. Parra, Maria Luisa T. Abesamis-Tiambeng, Charuwan Akewanlop, Ihor Vynnychenko, Virote Sriuranpong, Sirshendu Roy, Eduardo Patricio Yanez Ruiz, Abhijit Barve, Cornelius F. Waller 

The Breast: Published: March 31, 2021

Background

Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3 HERITAGE trial demonstrated equivalent overall response rate (ORR) with trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with HER2-positive metastatic breast cancer receiving chemotherapy. We now present the correlation of ORR with progression-free survival (PFS) for maintenance monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and the safety, tolerability, and immunogenicity.

Methods

HERITAGE is a multicenter, double-blind, randomized, parallel-group, phase 3 study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab in combination with taxane followed by continued monotherapy until disease progression. The analysis included PFS at 48 weeks to support the primary efficacy endpoint of ORR and safety, tolerability, and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance monotherapy.

Results

Of 500 randomized patients, 342 entered the monotherapy phase; 214 patients received ≥48 weeks of treatment. There were no statistically significant differences between PFS, ORR, or interim overall survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was highly correlated with week 48 PFS (rb = 0.75). Cumulative treatment-emergent adverse events (TEAEs) and serious AEs were similar in both groups, with few grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks.

Conclusion

The correlation between ORR and PFS supports the design of first-line metastatic trials assessing biosimilar trastuzumab. Overall, trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy, including ORR and PFS, in combination with a taxane followed by monotherapy.

Anticancer Effects of Radiation Therapy Combined with Polo-Like Kinase 4 (PLK4) Inhibitor CFI-400945 in Triple Negative Breast Cancer

 

Anticancer Effects of Radiation Therapy Combined with Polo-Like Kinase 4 (PLK4) Inhibitor CFI-400945 in Triple Negative Breast Cancer

by Armen Parsyan, Jennifer Cruickshank, Kelsey Hodgson, Drew Wakeham, Sierra Pellizzari, Vasudeva Bhat, David W. Cescon 

The Breast: Published:March 31, 2021

Highlights

The first in class inhibitor of PLK4, CFI-400945, exhibits synergistic effects with radiation in cell line and patient-derived organoids in vitro. In MDA-MB-231 xenografts, CFI-400945 sensitizes to ionizing radiation and significantly improves survival to tumour endpoint compared to single agent treatments.

Abstract

Development of novel multimodality radiotherapy treatments in metastatic breast cancer, especially in the most aggressive triple negative (TNBC) subtype, is of significant clinical interest. Here we show that a novel inhibitor of Polo-Like Kinase 4 (PLK4), CFI-400945, in combination with radiation, exhibits a synergistic anti-cancer effect in TNBC cell lines and patient-derived organoids in vitro and leads to a significant increase in survival to tumor endpoint in xenograft models in vivo, compared to control or single-agent treatment. Further preclinical and proof-of-concept clinical studies are warranted to characterize molecular mechanisms of action of this combination and its potential applications in clinical practice.

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

 

Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

by Junsheng Zhang, Ciqiu Yang, Chuqian Lei, Yi Zhang, Fei Ji, Hongfei Gao, Mei Yang, Liulu Zhang, Jieqing Li, Teng Zhu, Weiping Li, Xiaosheng Zhuang, Kun Wang 

The Breast: Published: March 31, 2021

Background

Previous studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC.

Methods

Surveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models.

Results

A total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR=0.76, 95%CI: 0.59-0.97, p=0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR=0.72, 95%CI: 0.53-0.96, p=0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage.

Conclusion

BCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.

Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study

 

Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study

 

by Hope S Rugo, Florence Lerebours, Eva Ciruelos, Pamela Drullinsky, Manuel Ruiz-Borrego, Patrick Neven, Yeon Hee Park, Aleix Prat, Thomas Bachelot, Dejan Juric, Nicholas Turner, Nickolas Sophos, Juan Pablo Zarate, Christina Arce, Yu-Ming Shen, Stuart Turner, Hemanth Kanakamedala, Wei-Chun Hsu, Stephen Chia 

 

The Lancet Oncology: VOLUME 22, ISSUE 4, P489-498, APRIL 01, 2021

 

Background

Alpelisib, a PI3Kα-selective inhibitor and degrader, plus fulvestrant showed efficacy in hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer in SOLAR-1; limited data are available in the post-cyclin-dependent kinase 4/6 inhibitor setting. BYLieve aimed to assess alpelisib plus endocrine therapy in this setting in three cohorts defined by immediate previous treatment; here, we report results from cohort A.

Methods

This ongoing, phase 2, multicentre, open-label, non-comparative study enrolled patients with hormone receptor-positive, HER2-negative, advanced breast cancer with tumour PIK3CA mutation, following progression on or after previous therapy, including CDK4/6 inhibitors, from 114 study locations (cancer centres, medical centres, university hospitals, and hospitals) in 18 countries worldwide. Participants aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 2 or less, with no more than two previous anticancer treatments and no more than one previous chemotherapy regimen, were enrolled in three cohorts. In cohort A, patients must have had progression on or after a CDK4/6 inhibitor plus an aromatase inhibitor as the immediate previous treatment. Patients received oral alpelisib 300 mg/day (continuously) plus fulvestrant 500 mg intramuscularly on day 1 of each 28-day cycle and on day 15 of cycle 1. The primary endpoint was the proportion of patients alive without disease progression at 6 months per local assessment using Response Evaluation Criteria in Solid Tumors, version 1.1, in patients with a centrally confirmed PIK3CA mutation. This trial is registered with ClinicalTrials.gov, NCT03056755.

Findings

Between Aug 14, 2017, and Dec 17, 2019 (data cutoff), 127 patients with at least 6 months' follow-up were enrolled into cohort A. 121 patients had a centrally confirmed PIK3CA mutation. At data cutoff, median follow-up was 11·7 months (IQR 8·5–15·9). 61 (50·4%; 95% CI 41·2–59·6) of 121 patients were alive without disease progression at 6 months. The most frequent grade 3 or worse adverse events were hyperglycaemia (36 [28%] of 127 patients), rash (12 [9%]), and rash maculopapular (12 [9%]). Serious adverse events occurred in 33 (26%) of 127 patients. No treatment-related deaths were reported.

Interpretation

BYLieve showed activity of alpelisib plus fulvestrant with manageable toxicity in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer, after progression on a CDK4/6 inhibitor plus an aromatase inhibitor.

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

 

Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial

 

by Eric P Winer, Oleg Lipatov, Seock-Ah Im, Anthony Goncalves, Eva Muñoz-Couselo, Keun Seok Lee, Peter Schmid, Kenji Tamura, Laura Testa, Isabell Witzel, Shoichiro Ohtani, Nicholas Turner, Stefania Zambelli, Nadia Harbeck, Fabrice Andre, Rebecca Dent, Xuan Zhou, Vassiliki Karantza, Jaime Mejia, Javier Cortes, KEYNOTE-119 investigators 

 

The Lancet Oncology:  VOLUME 22, ISSUE 4, P499-511, APRIL 01, 2021

 

Background

Pembrolizumab showed durable antitumour activity and manageable safety in metastatic triple-negative breast cancer in the single-arm KEYNOTE-012 and KEYNOTE-086 trials. In this study, we compared pembrolizumab with chemotherapy for second-line or third-line treatment of patients with metastatic triple-negative breast cancer.

Methods

KEYNOTE-119 was a randomised, open-label, phase 3 trial done at 150 medical centres (academic medical centres, community cancer centres, and community hospitals) in 31 countries. Patients aged 18 years or older, with centrally confirmed metastatic triple-negative breast cancer, Eastern Cooperative Oncology Group performance status of 0 or 1, who had received one or two previous systemic treatments for metastatic disease, had progression on their most recent therapy, and had previous treatment with an anthracycline or taxane were eligible. Patients were randomly assigned (1:1) using a block method (block size of four) and an interactive voice-response system with integrated web-response to receive intravenous pembrolizumab 200 mg once every 3 weeks for 35 cycles (pembrolizumab group), or to single-drug chemotherapy per investigator's choice of capecitabine, eribulin, gemcitabine, or vinorelbine (60% enrolment cap for each; chemotherapy group). Randomisation was stratified by PD-L1 tumour status (positive [combined positive score (CPS) ≥1] vs negative [CPS <1]) and history of previous neoadjuvant or adjuvant treatment versus de-novo metastatic disease at initial diagnosis. Primary endpoints were overall survival in participants with a PD-L1 combined positive score (CPS) of 10 or more, those with a CPS of 1 or more, and all participants; superiority of pembrolizumab versus chemotherapy was tested in all participants only if shown in those with a CPS of one or more. The primary endpoint was analysed in the intention-to-treat population; safety was analysed in the all-subjects-as-treated population. This Article describes the final analysis of the trial, which is now completed. This trial is registered with ClinicalTrials.gov, number NCT02555657.

Findings

From Nov 25, 2015, to April 11, 2017, 1098 participants were assessed for eligibility and 622 (57%) were randomly assigned to receive either pembrolizumab (312 [50%]) or chemotherapy (310 [50%]). Median study follow-up was 31·4 months (IQR 27·8–34·4) for the pembrolizumab group and 31·5 months (27·8–34·6) for the chemotherapy group. Median overall survival in patients with a PD-L1 CPS of 10 or more was 12·7 months (95% CI 9·9–16·3) for the pembrolizumab group and 11·6 months (8·3–13·7) for the chemotherapy group (hazard ratio [HR] 0·78 [95% CI 0·57–1·06]; log-rank p=0·057). In participants with a CPS of 1 or more, median overall survival was 10·7 months (9·3–12·5) for the pembrolizumab group and 10·2 months (7·9–12·6) for the chemotherapy group (HR 0·86 [95% CI 0·69–1·06]; log-rank p=0·073). In the overall population, median overall survival was 9·9 months (95% CI 8·3–11·4) for the pembrolizumab group and 10·8 months (9·1–12·6) for the chemotherapy group (HR 0·97 [95% CI 0·82–1·15]). The most common grade 3–4 treatment-related adverse events were anaemia (three [1%] patients in the pembrolizumab group vs ten [3%] in the chemotherapy group), decreased white blood cells (one [<1%] vs 14 [5%]), decreased neutrophil count (one [<1%] vs 29 [10%]), and neutropenia (0 vs 39 [13%]). 61 (20%) patients in the pembrolizumab group and 58 (20%) patients in the chemotherapy group had serious adverse events. Three (<1%) of 601 participants had treatment-related adverse events that led to death (one [<1%] in the pembrolizumab group due to circulatory collapse; two [1%] in the chemotherapy group, one [<1%] due to pancytopenia and sepsis and one [<1%] haemothorax).

Interpretation

Pembrolizumab did not significantly improve overall survival in patients with previously treated metastatic triple-negative breast cancer versus chemotherapy. These findings might inform future research of pembrolizumab monotherapy for selected subpopulations of patients, specifically those with PD-L1-enriched tumours, and inform a combinatorial approach for the treatment of patients with metastatic triple-negative breast cancer.

Frequency and Outcomes of Benign Breast Biopsies in Trans Women: a Nationwide Cohort study

 

Frequency and Outcomes of Benign Breast Biopsies in Trans Women: a Nationwide Cohort study

 

by Christel JM. de Blok, Benthe Dijkman, Chantal M. Wiepjes, Inge RHM. Konings, Koen Dreijerink, Ellis Barbé, Martin den Heijer 

 

The Breast: VOLUME 57, P118-122, JUNE 01, 2021 (Published: March 25, 2021)

 

 

No literature is available on the benign versus malignant breast lesion ratio in trans women (male sex assigned at birth, female gender identity). As hormone treatment in trans women results in breast tissue histologically comparable with cis (non-trans) women, breast pathology may be expected. Previously, an increased breast cancer risk compared with cis men have been observed. We aimed to investigate the frequency and outcomes of breast biopsies in trans women. Therefore, we retrospectively examined the medical files of 2616 trans women. To gain data on breast lesions, we linked our cohort to a national pathology database. In this study we found that 126 people (5%) had one or more breast biopsies (n = 139). Of these, 21 trans women had a breast biopsy before the start of hormone treatment, and 53 after the start of hormone treatment. Breast biopsies were performed predominantly because of abnormalities during physical examination (37%, n = 51/139 biopsies), or because of capsular formation or contraction (28%, n = 16/57 biopsies) in trans women with breast implants. The most common breast lesions after the start of hormone treatment were fibroadenomas (n = 20), breast cancer (n = 6), fibrosis (n = 5), cysts (n = 4), and infections (n = 4). The benign versus malignant breast biopsy ratio was 88:12, which is comparable to the ratio in cis women (90:10). This study shows breast lesions in a limited number of trans women. Since the indications and outcomes of biopsies in trans women were similar to those in cis women, it seems reasonable to follow breast care guidelines as developed for cis women.

The applicability of Magseed® for Targeted Axillary Dissection in breast cancer patients treated with neoadjuvant chemotherapy

 

The applicability of Magseed® for Targeted Axillary Dissection in breast cancer patients treated with neoadjuvant chemotherapy

by Reitsamer R, Peintinger F, Forsthuber E, Sir A 

The Breast VOLUME 57, P113-117, JUNE 01, 2021 (Published: March 25, 2021)

Background

Targeted axillary dissection (TAD), the combination of sentinel lymph node biopsy (SLNB) and targeted lymph node biopsy (TLNB), can reduce the false negative rates of sentinel node biopsy alone dramatically in breast cancer patients, who received neoadjuvant chemotherapy (NAC). However methods for TAD are still under investigation.

Methods

Magseed®, a non-radioactive magnetic marker was used to mark the biopsied positive TLN after NAC. The SLNB with the standard technetium-based method and the selective TLNB with Magseed® localization were performed in 40 patients. The TLNs were identified with the Sentimag® probe and excised in all patients. Specimen x-ray was performed to confirm the Magseed® within the prior to NAC biopsied and clipped lymph node.

Results

The TLN identification rate was 100% (40/40), the SLN identification rate was 82.5% (33/40), the concordance rate between the TLN and the SLN was 65% (26/40). Complications according Magseed® deployment or identification could not be observed.

Conclusion

Magseed® is a reliable and feasible marker for the identification of TLNs after NAC.

Splitting the Difference: Using Synthetic and Biologic Mesh to Decrease Cost in Prepectoral Immediate Implant Breast Reconstruction

 

Splitting the Difference: Using Synthetic and Biologic Mesh to Decrease Cost in Prepectoral Immediate Implant Breast Reconstruction

 

by Karp, Nolan S.; Salibian, Ara A. 

 

Plastic and Reconstructive Surgery: March 2021 - Volume 147 - Issue 3 - p 580-584

 

Prepectoral breast reconstruction has minimized morbidity and dynamic deformities associated with submuscular implant-based breast reconstruction. However, reliance on implant coverage with acellular dermal matrix in immediate implant reconstruction remains limited by high material costs. The authors describe a technique in which anterior implant coverage in prepectoral reconstruction is split into acellular dermal matrix inferolaterally and synthetic, absorbable mesh superiorly. Use of acellular dermal matrix inferiorly provides coverage and reinforces the inframammary fold, whereas the absorbable mesh is trimmed and sutured to the acellular dermal matrix at the appropriate tension to support the implant and relieve pressure on mastectomy flaps. A retrospective review was performed on all consecutive prepectoral one-stage breast reconstructions using this technique at a single institution. Patient demographics, mastectomy and reconstruction characteristics, reconstructive outcomes, and cost of support materials were queried and analyzed. Eleven patients (21 breasts) underwent prepectoral immediate implant reconstruction with Vicryl and acellular dermal matrix anterior coverage. Average mastectomy weight was 775.8 g. Smooth, round cohesive implants were used in all cases and average implant size was 514.5 ml. Overall complication rates were low and included one minor infection (4.8 percent) and one case of minor mastectomy flap and partial nipple necrosis each (4.8 percent). Calculated cost savings of Vicryl and acellular dermal matrix anterior coverage was up to $3415 in unilateral and $6830 in bilateral cases. Prepectoral breast reconstruction using acellular dermal matrix inferiorly and Vicryl mesh superiorly is a safe technique that decreases material costs associated with support materials and allows the surgeon to precisely control the implant pocket and position. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Does the Textured-Type Tissue Expander Affect the Outcomes of Two-Stage Prosthetic Breast Reconstruction? A Propensity Score Matching Analysis between Macrotextured and Microtextured Expanders

Does the Textured-Type Tissue Expander Affect the Outcomes of Two-Stage Prosthetic Breast Reconstruction? A Propensity Score Matching Analysis between Macrotextured and Microtextured Expanders

 

by Lee, Kyeong-Tae; Park, Hae Yeon; Jeon, Byung-Joon; Mun, Goo-Hyun; Bang, Sa Ik; Pyon,expander Jai Kyong 

 

Plastic and Reconstructive Surgery: March 2021 - Volume 147 - Issue 3 - p 545-555

 

Background:

 

In two-stage prosthetic breast reconstruction, two types of tissue expanders are used for the first stage: microtextured Siltex and macrotextured Biocell. Despite emerging concerns regarding the safety of macrotextured prostheses, the association between the use of macrotextured expanders and adverse outcomes remains unknown clinically. This study aimed to evaluate potential impacts of the type of tissue expander on the long-term outcomes of implant-based breast reconstruction.

 

Methods:

 

Patients who underwent immediate two-stage tissue expander/implant breast reconstruction between 2014 and 2018 were evaluated and categorized into two groups according to the expander type. Those two were propensity score matched for baseline characteristics and compared for complication rates after the first- and second-stage operations. The impacts of several variables, including type of tissue expander used, on outcomes were assessed using multivariable logistic regression analyses.

 

Results:

 

Of the 1391 cases in 1294 patients, 276 pairs (552 cases) were successfully propensity score matched. In the first-stage operation, the macrotextured group showed a significantly shorter drain indwelling period and lower rate of seroma than the microtextured group. These differences retained influences after adjusting for other variables. Incidence rates of other complications were similar between the groups. Regarding the second-stage operation, the use of macrotextured expanders showed a significant association, with an increased rate of severe capsular contracture on the multivariable analyses in cases using textured implants. Development of other complications was not affected by the expander type.

 

Conclusion:

 

The type of tissue expander might influence the outcomes of two-stage implant-based breast reconstruction, and generally acceptable safety of both microtextured and macrotextured expanders was shown. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III. 

Clinical predictors of cardiac toxicity in HER2-positive early breast cancer patients treated with adjuvant s.c. versus i.v. trastuzumab

 Clinical predictors of cardiac toxicity in HER2-positive early breast cancer patients treated with adjuvant s.c. versus i.v. trastuzumab

by Rita De Sanctis, Laura Giordano, Federica D’Antonio, Elisa Agostinetto, Arianna Marinello, Daniela Guiducci, Giovanna Masci, Agnese Losurdo, Monica Zuradelli, Rosalba Torrisi, Armando Santoro 

 

The Breast: VOLUME 57, P80-85, JUNE 01, 2021 (Published: March 17, 2021)

 

Background

Few data are available about real-life cardiotoxicity associated with s.c. versus i.v. trastuzumab treatment of early-stage, HER2-positive breast cancer, and little is known about its predisposing factors.

Patients and methods

We retrospectively reviewed data of 363 adult patients treated with adjuvant trastuzumab for HER2-positive breast cancer. Univariate statistical analysis was performed, and a multivariable logistic model was developed to identify independent risk factors of cardiac toxicity.

Results

Within 5 years, the overall incidence of events meeting our criteria was 11.8%, and an early discontinuation of trastuzumab was recorded in 20 patients (5.5%). No cases of congestive heart failure occurred, neither multiple events per patient were observed. A total of 184 patients received i.v. and 179 received s.c. trastuzumab. Compared with the s.c. formulation, a higher cardiotoxicity rate for the i.v. administration (15.2% vs 8.4%) was found, and particularly in those patients with cardiovascular risk factors (19.3% vs 8.7%), at the univariate and multivariate analyses. Although more patients with prior anthracycline-based chemotherapy experienced cardiac events, the association of this therapy with cardiac events was not significant. The incidence of cardiac events was not influenced by anthropometric data (e.g. body mass index) or a diagnosis of diabetes mellitus. 5-year event-free survival was 91.7% in the overall population; event-free survival rates were similar between the s.c. and the i.v. groups.

Conclusion

Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients.

Retrospective study of malignant phyllodes tumors of the breast: younger age, prior fibroadenoma surgery, malignant heterologous elements and surgical margins may predict recurrence

 

Retrospective study of malignant phyllodes tumors of the breast: younger age, prior fibroadenoma surgery, malignant heterologous elements and surgical margins may predict recurrence

 

by Yang Li, Yixuan Song, Ronggang Lang, Lu Shi, Shuang Gao, Hong Liu, Ping Wang 

 

The Breast: VOLUME 57, P62-70, JUNE 01, 2021 (Published: March 16, 2021)

 

Purpose

The potential recurrence rate of malignant phyllodes tumors (MPTs) of the breast is high, and the prognostic factors are still unclear. We therefore aim to study the factors affecting the outcome of MPTs.

Methods

A retrospective review of MPT patients treated from 2006 to 2020 at our institution was conducted. Univariate and multivariate Cox proportional hazard models were used to examine the influence of different variables on RFS. Moreover, significant prognostic factors were combined to construct the nomogram to predict the probability of relapse occurring in MPT patients. The 5-year and 10-year RFS rates were estimated using the Kaplan–Meier method.

Results

During the study period, 188 MPT patients were identified. The presence of malignant heterologous elements was observed in 23 (12.2%) patients with MPT, and the patients with malignant heterologous elements who received chemotherapy had longer RFS, which could reduce the risk of recurrence (p = 0.022). Recurrence occurred in 56/188 (29.8%) patients, of whom 47 experienced local recurrence and 11 experienced distant metastases. The 5-year and 10-year cumulative RFS rates were 77.5% and 70.1%, respectively. Age (p = 0.041), fibroadenoma surgery history (p = 0.004), surgical margins (p = 0.001) and malignant heterologous elements (p < 0.001) were independent risk factors for postoperative RFS. Subsequently, a nomogram was built, with a C-index of 0.64 (95% CI: 0.629–0.661), to predict the risk of recurrence.

Conclusion

The results of this study showed that younger age, fibroadenoma surgery history, malignant heterologous elements and surgical margins <1 cm predict a higher incidence of recurrence in MPT patients. Patients with malignant heterologous elements treated with chemotherapy could have a reduced risk of recurrence.

 

First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: a real-world study

 

First- and second-line treatment strategies for hormone-receptor (HR)-positive HER2-negative metastatic breast cancer: a real-world study

by Debora Basile, Lorenzo Gerratana, Carla Corvaja, Giacomo Pelizzari, Giorgia Franceschin, Elisa Bertoli, Lorenza Palmero, Diego Zara, Martina Alberti, Silvia Buriolla, Lucia Da Ros, Marta Bonotto, Mauro Mansutti, Simon Spazzapan, Marika Cinausero, Alessandro Marco Minisini, Gianpiero Fasola, Fabio Puglisi 

The Breast: VOLUME 57, P104-112, JUNE 01, 2021 (Published: March 11, 2021)

Background

Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L.

Materials and methods

717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated.

Results

At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi.

Conclusion

Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines.