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.

 

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.

Breast Surgery Bulletin - October 2022

 

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study

 

by Mariana-Felicia Sandor, Beatrice Schwalbach, Viktoria Hofmann, Simona-Elena Istrate, Zlatna Schuller, Elena Ionescu, Sara Heiman, Moira Ragazzi, Michael P. Lux 

 

The Breast: Published: October 05, 2022

 

Introduction

Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10–40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device.

Materials and methods

40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated.

Results

The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins.

Conclusion

The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase–III–trial.

 

 

 

 

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study

by Mattea Reinisch, Michael Untch, Rolf Mahlberg, Toralf Reimer, Thomas Hitschold, Frederik Marmé, Mustafa Aydogdu, Sabine Schmatloch, Hans-Joachim Lück, Marcus Schmidt, Ekkehart Ladda, Bruno Valentin Sinn, Peter Klare, Wolfgang Janni, Christian Jackisch, Carsten Denkert, Sabine Seiler, Thomas Göhler, Laura Michel, Nicole Burchardi, Elmar Stickeler, Julia Rey, Nicole Klutinus, Volker Möbus, Sibylle Loibl 

The Breast: Published: October 05, 2022

Background

Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients.

Methods

After surgery, patients were randomised to receive either subcutaneous trastuzumab into the thigh or into the abdominal wall (AW). Patient preferences were evaluated using validated questionnaires (PINT). Primary objectives of this multicentre, non-blinded, randomised substudy of the GAIN-2 study were to investigate pharmacokinetics of the injection into the thigh versus AW and to determine patients' preferences of either administration site versus the previously received intravenous application.

Results

226 patients were randomised and 219 patients (thigh: N = 110; AW: N = 109) formed the modified intent-to-treat (mITT). Overall, 83.5% (out of N = 182 with information about patients’ preference) preferred subcutaneous over previous intravenous application or had no preference. Preference was similar between both administration sites (thigh: 80.6%; AW: 86.5; p = 0.322). Pharmacokinetic analysis included 30 patients. Geometric means of Cmax and AUC0-21d were higher in thigh than in AW group (geometric mean ratio with body weight adjustment: Cmax: 1.291, 90%-CI 1.052–1.584; AUC0-21d: 1.291, 90%-CI 1.026–1.626). Safety profile was in line with previous reports of subcutaneous trastuzumab.

Conclusion

Subcutaneous trastuzumab into the thigh showed an approximately 30% higher bioavailability. Injections were well tolerated and preferred over intravenous administration. The subcutaneous injection into the thigh should remain the standard of care.

 

 

Adjuvant endocrine therapy in patients with estrogen receptor-low positive breast cancer: A prospective cohort study

 

by Yuxin Xie, Libo Yang, Yanqi Wu, Hong Zheng, Qiheng Gou 

 

The Breast: Published: September 29, 2022

 

Background

Little is known about the benefits of adjuvant endocrine therapy (ET) in low ER-positive breast cancer (1%–10%) patients. We analyzed the association between ET and breast cancer-specific survival (BCSS) in these patients with respect to the regimen and the duration of ET.

Methods

Patients were classified into three groups based on the regimen and duration of ET. The regimens included aromatase inhibitor (AI) monotherapy or sequential tamoxifen followed by an AI (AI/T + AI), or only tamoxifen and no ET. The duration of ET included 2–3 years and >3 years. Multivariate Cox regression analysis was employed to calculate the hazard ratios (HRs) with 95% confidence intervals (CIs).

Results

Of the 10,696 patients diagnosed with breast cancer between 2010 and 2020, 407 women were identified with ER-low positive disease and met the inclusion criteria. During a median follow-up of 5.2 years, patients who received ET improved BCSS. Of them, those with AI/T + AI had increased BCSS compared to patients without ET, after adjusting for demographics and tumor characteristics, especially in ER-low/HER-2-positive breast cancer. After additional adjustment for treatment mode, the association maintained a similar trend. Patients who received >3 years of ET was associated with a better DFS. There was no significant difference in BCSS between patients with 2–3 years and >3 years of ET.

Conclusion

For ER-low patients, findings suggest that ET with AI/T + AI may be a reasonable treatment alternative. This effect should be assessed in randomized studies.