Breast Surgery Bulletin - November 2022

 

Mondor's disease of the breast: A cutaneous thromboembolic manifestation of Covid-19?

by Lorna Renshaw, J Michael Dixon, Julia Anderson, Arran K. Turnbull 

The Breast: VOLUME 66, P305-309, DECEMBER 01, 2022

Background

Mondor's disease is a rare disorder characterised by thrombosis of superficial veins within the subcutaneous tissue of the breast and other organs. While factors such as trauma, infection, physical exertion, breast cancer and breast surgery have been implicated, in the majority no cause is identified.

Patients

Twenty patients presented with a clinical diagnosis of Mondor's disease to the Edinburgh Breast Services in 2020. We present the etiopathogenic data as well as clinical and imaging diagnostic findings.

Results

During 2020, the annual incidence of Mondor's disease, in the UK's largest breast unit, increased five-fold compared to data from the previous year. This variation in the frequency of cases corresponded to trends in the frequency of Covid-19 infection during the pandemic. None of the patients had diagnosed COVID and few had any known etiopathogenic causes for their Mondor's.

Conclusion

Several recent studies have provided evidence for links between Covid-19 and thromboembolic events. Isolated reports have proposed a link between Covid-19 and Mondor's disease of the penis. Here we present data on a large series of Mondor's disease of the breast supporting a link between breast Mondor's and Covid-19.

 

Real-world data of HER2-low metastatic breast cancer: A population based cohort study

 

by Emily I. Holthuis, Gerard T. Vondeling, Josephina G. Kuiper, Vincent Dezentjé, Mats Rosenlund, Jetty A. Overbeek, Carolien H.M. van Deurzen 

 

The Breast: VOLUME 66, P278-284, DECEMBER 01, 2022

 

Background

With the introduction of investigational human epidermal growth factor receptor 2 (HER2) targeting treatments, thorough understanding of breast cancer with different HER2 expression levels is critical. The aim of this study was to compare clinicopathologic characteristics and survival of patients with metastatic breast cancer according to the level of HER2 expression.

Methods

Women with distant metastatic breast cancer during 2008–2016 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO Database Network. Breast cancer samples were categorised as HER2 immunohistochemistry score 0 (IHC0), HER2-low or HER2+.

Results

Among women with hormone receptor (HR) positive metastatic breast cancer (n = 989), 373 (38%) cancers were HER2 IHC0, 472 (48%) were HER2-low and 144 (15%) were HER2+. Among HR negative patients (n = 272), the proportion of HER2 IHC0, HER2-low and HER2+ was 110 (40%), 104 (38%) and 58 (21%) respectively.

Within the HR + cohort, patients with HER2 IHC0 or HER2-low cancer were significantly older compared to HER2+ patients. This age difference was not seen in the HR-cohort. The localisation of distant metastases differed significantly between HER2 IHC0 or HER2-low versus HER2+ cases. Survival rates did not differ markedly by subtypes.

Conclusion

Substantial proportion of patients had a HER2-low breast cancer. No clear differences in survival were found when comparing HER2 and HR status. Getting more granular insights in the level of HER2 expression and addressing HER2-low as a separate category could help to assess the impact of emerging treatment strategies. Therefore, more detailed information on HER2 expression should be routinely reported.

 

Clinical Relevance of Sensory Nerve Coaptation in DIEP Flap Breast Reconstruction Evaluated Using the BREAST-Q

 

By Bijkerk, Ennie; Beugels, Jop; van Kuijk, Sander M. J.; Lataster, Arno; van der Hulst, René R. W. J.; Tuinder, Stefania M. H.

 

Plastic and Reconstructive Surgery: November 2022 - Volume 150 - Issue 5 - p 959e-969e

 

Background: 

Sensory nerve coaptation in autologous breast reconstruction positively affects sensory recovery in the reconstructed breast. However, patient-reported outcomes are lacking and no conclusions on the clinical relevance of nerve coaptation could be drawn. The aim of this study was to evaluate the clinical relevance of nerve coaptation in deep inferior epigastric perforator (DIEP) flap breast reconstruction.

Methods: 

A prospective cohort study was conducted of patients undergoing innervated or noninnervated DIEP flap breast reconstruction between August of 2016 and August of 2018. Patients completed a BREAST-Q questionnaire at a minimum of 12 months’ follow-up in combination with either a preoperative questionnaire or a questionnaire at 6 months’ follow-up. The physical well-being of the chest domain was the primary outcome and patients answered additional sensation-specific questions. Sensation was measured using Semmes-Weinstein monofilaments.

Results: 

In total, 120 patients were included (65 innervated and 55 noninnervated reconstructions). A clinically relevant difference was found in BREAST-Q scores in favor of patients with innervated reconstructions in general and for delayed reconstructions specifically. Patients with sensate breast reconstruction more often reported better and pleasant sensation.

Conclusions: 

This study demonstrated that nerve coaptation in DIEP flap breast reconstruction, specifically in delayed reconstruction, resulted in clinically relevant improved patient-reported outcomes on the physical well-being of the chest domain of the BREAST-Q and that better sensation was perceived. However, the BREAST-Q does not address sensation adequately, and the introduction and validation of new scales is required to confirm the clinical relevance of nerve coaptation reliably.

 

Adjuvant trastuzumab without chemotherapy for treating early HER2-positive breast cancer in older patients: A propensity score-adjusted analysis of a prospective cohort study

 

by RESPECT study group 

The Breast: VOLUME 66, P245-254, DECEMBER 01, 2022

Purpose

To gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT).

Methods

Patients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed.

Results

We enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15–9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32–26.2, P < 0.0001). There were no significant intergroup differences in the proportions of patients showing HRQoL deterioration at 36 months (P = 0.717).

Conclusion

Trastuzumab-treated patients had better prognoses than patients not treated with trastuzumab without deterioration of HRQoL. Trastuzumab monotherapy could be considered for older patients who reject chemotherapy.

 

PARP-inhibitors for BRCA1/2-related advanced HER2-negative breast cancer: A meta-analysis and GRADE recommendations by the Italian Association of Medical Oncology

 

by Federica Miglietta, Michela Cinquini, Maria Vittoria Dieci, Laura Cortesi, Carmen Criscitiello, Filippo Montemurro, Lucia Del Mastro, Alberto Zambelli, Laura Biganzoli, Alessia Levaggi, Chiara Delle Piane, Caterina Marchiò, Massimo Calabrese, Lucio Fortunato, Pierfrancesco Franco, Bruno Meduri, Veronica Andrea Fittipaldo, Stefania Gori 

 

The Breast: VOLUME 66, P293-304, DECEMBER 01, 2022

 

Background

Approximately 5–10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negative (HER2-) advanced BC based on the results from the phase III OlympiAd and EMBRACA trials.

Methods

The panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guidelines on Breast Cancer addressed two critical clinical questions, adopting the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach and the Evidence to Decision framework (EtD), to develop recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related triple-negative (clinical question 1) and hormone receptor-positive (HR+)/HER2- (clinical question 2) advanced BC.

Results

Two studies were eligible (OlympiAd and EMBRACA). For both clinical questions, the Panel judged the benefit/harm balance probably in favor of the intervention, given the favorable impact in terms of PFS, ORR, and QoL at an acceptable cost in terms of toxicity; the overall certainty of the evidence was low. The panel's final recommendations were conditional in favor of PARP-inhibitors over single-agent chemotherapy in both HR+/HER2-and triple-negative BC. Finally, the Panel identified and discussed areas of uncertainty calling for further exploration.

Conclusions

The Panel of AIOM BC Clinical Practice Guideline provided clinical recommendations on the use of PARP-inhibitors, with respect to single-agent chemotherapy, in patients with BRCA-related HER2-advanced BC by adopting the GRADE methodology.

 

Acinic cell carcinoma of the breast: A comprehensive review

 

by Azra Ajkunic, Faruk Skenderi, Nada Shaker, Saghir Akhtar, Janez Lamovec, Zoran Gatalica, Semir Vranic 

 

The Breast: VOLUME 66, P208-216, DECEMBER 01, 2022

 

Acinic cell carcinoma of the breast is a rare special subtype of breast cancer in the category of salivary gland-type tumors. It is morphologically similar to acinic cell carcinomas of salivary glands and pancreas and has a triple-negative phenotype (estrogen receptor-negative, progesterone receptor-negative, and Her-2/neu negative). Its molecular genomic features are more similar to triple-negative breast cancer of no special type than to its salivary gland counterpart. However, the clinical course of the mammary acinic cell carcinoma appears to be less aggressive than the usual triple-negative breast carcinomas. This review comprehensively summarizes the current literature on the clinicopathologic, immunohistochemical, and molecular features of this rare and distinct subtype of breast cancer.

 

Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer

 

by Elie Rassy, Layal Rached, Barbara Pistilli 

 

The Breast: VOLUME 66, P217-226, DECEMBER 01, 2022

 

The identification of the HER2 alteration as an actionable oncogenic driver in breast cancer has propelled the development of HER-targeting monoclonal antibodies (mAb) such as trastuzumab and pertuzumab, which led to dramatic improvements in survival outcomes. Lately, the great strides made toward developing antibody-conjugation methods have led to the development of a new class of compelling compounds, the antibody-drug conjugates (ADCs) targeting HER2 which have profoundly transformed the treatment landscape of breast cancer. HER2-targeting ADCs, trastuzumab-emtansine and trastuzumab-deruxtecan, have improved the overall survival in the second and third-line settings with manageable adverse events. Other HER2-targeting ADCs using novel technological advances in the antibody, linker and/or payload conception have shown promising activity in preclinical and clinical studies and some of them are now being evaluated in larger clinical trials. Multiple challenges still impede the success of ADCs in breast cancer namely the lack of a comprehensive understanding of resistance mechanisms as well as the mechanisms of action of ADCs in special subgroups of patients such as those with low or ultra-low HER2 expression and patients with brain or leptomeningeal metastases (BM). In this framework, we review the approved indications and ongoing trials for HER2-targeting ADCs, across patient subgroups, including those with BM and discuss the associated potential mechanisms of action and resistance. Last, we provide an overview of the future perspectives involving HER2-targeting ADCs in breast cancer.

 

Antibody-drug conjugates targeting Trop-2: Clinical developments in early breast cancer therapy

 

by Jae Ho Jeong, Sung-Bae Kim / October 26, 2022

 

The Breast: VOLUME 66, P199-203, DECEMBER 01, 2022

 

Although breast cancer has a good prognosis compared with various cancers, metastatic breast cancer has an aggressive disease course and remains incurable. Therefore, treatment of early breast cancer to prevent recurrence and metastasis is crucial. Recently, the development of anti-cancer drugs, such as targeted agents and immuno-oncology, has been accelerating. Antibody-drug conjugates (ADCs) are also building a new paradigm. Particularly, ADCs targeting Trop-2 were approved for their efficacy in metastatic triple-negative breast cancer patients who received ≥2 prior systemic therapies and showed significant results in heavily pretreated hormone receptor-positive/HER2-negative breast cancer. In this brief review, we provide an overview of ongoing clinical trials of ADCs targeting Trop-2 in early breast cancer, specifically sacituzumab govitecan.

 

Closed-Incision Negative-Pressure Therapy Reduces Donor-Site Surgical Wound Dehiscence in DIEP Flap Breast Reconstructions: A Randomized Clinical Trial

 

by Muller-Sloof, Emmy; de Laat, Erik; Kenç, Onur; Kumaş, Ali; Vermeulen, Hester; Hummelink, Stefan; Ulrich, Dietmar J. O. 

 

Plastic and Reconstructive Surgery: October 2022 - Volume 150 - Issue - p 38S-47S

 

Background: 

In breast reconstruction operations, surgical wound dehiscence is a serious complication that generates a significant burden on patients and health care systems. There are indications that postoperative treatment with closed-incision negative-pressure therapy has been associated with reduced wound dehiscence rates. This randomized clinical trial examines the effect of closed-incision negative-pressure application on abdominal donor-site surgical wound dehiscence in low- and high-risk patients undergoing breast reconstruction with a deep inferior epigastric perforator flap.

Methods: 

Eighty eligible women, stratified as low- or high-risk patients, were included and were randomized for treatment with either closed-incision negative-pressure or adhesive strips by drawing sealed, opaque envelopes. All surgeons were kept blinded for allocation. Primary outcomes were surgical wound dehiscence and surgical-site infection at the abdominal donor site on follow-up after 12 weeks. Secondary outcomes were seroma and hematoma formation. Five patients were excluded from the study because of insufficient exposure to the study treatment (n = 4) or major protocol deviation (n = 1).

Results: 

A total of 75 women, low-risk (n = 38) and high-risk (n = 37), received either closed-incision negative-pressure (n = 36) or adhesive strips (n = 39). Patients’ demographics did not differ significantly. Donor-site surgical wound dehiscence occurred in 23 patients; the absolute risk reduction was statistically significant (21.6 percent; 95 percent CI, 1.5 to 41.7 percent). No statistically significant differences were found in surgical-site infection or secondary outcomes.

Conclusion: 

In this randomized clinical trial, postoperative treatment with closed-incision negative-pressure therapy decreased the incidence of surgical wound dehiscence at the abdominal donor site in low- and high-risk deep inferior epigastric perforator flap breast reconstruction patients.

 

 

 

Inclusion of premenopausal women in breast cancer clinical trials

 

by Kelsey L. Corrigan, Ramez Kouzy, Joseph Abi Jaoude, Roshal R. Patel, Rachel M. Layman, Sharon H. Giordano, Wendy A. Woodward, Benjamin D. Smith, Simona F. Shaitelman, Ethan B. Ludmir 

 

The Breast:  VOLUME 66, P204-207, DECEMBER 01, 2022

 

Background

Patients with premenopausal breast cancer (PMBC) have been historically excluded from some clinical trials because of the limitations of using endocrine therapy (ET) in this population. We analyzed breast cancer randomized clinical trials (RCTs) to determine the rates of and factors associated with inclusion of PMBC patients to provide a benchmark for PMBC inclusion in RCTs moving forward.

Methods

Using ClinicalTrials.Gov, we identified breast cancer phase III RCTs and extracted inclusion criteria and patient enrollment information. Multiple binary logistic regression modeling was used to assess trial-related factors that were associated with PMBC patient inclusion.

Results

Of 170 breast cancer RCTs identified, 131 (77.1%) included PMBC patients. Sixty-five (38.2%) trials analyzed patients with hormone-receptor-positive (HR+) and HER2-negative (HER2-) breast cancer, of which 31 (47.7%) allowed for enrollment of PMBC patients. Lower rates of PMBC inclusion were seen in trials that studied HR+/HER2-patients (47.7% PMBC inclusion in HR+/HER2-trials vs. 94.3% in non-HR+/HER2-trials, aOR 0.07 [95% CI: 0.02–0.19], p < 0.001) and in trials that randomized or mandated ET (44.4% in ET trials vs. 83.2% in non-ET trials, aOR 0.21 [95% CI: 0.10–0.83], p = 0.02). Trials studying chemotherapy (CT) were associated with inclusion of PMBC patients (100% in CT trials vs. 70.5% in non-CT trials, a OR 14.02 [95% CI: 1.54–127.91], p = 0.01). All surgical and radiation therapy clinical trials allowed for the inclusion of PMBC patients in their eligibility criteria.

Conclusions

Breast cancer clinical trials should carefully select their enrollment criteria and consider inclusion of premenopausal patients when appropriate.