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.

 

 

Safety and efficacy of ribociclib plus letrozole in patients with HR+, HER2– advanced breast cancer: Results from the Spanish sub-population of the phase 3b CompLEEment-1 trial

 

The Breast: Published: September 27, 2022

 

Background

Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC) vs. ET alone.

Methods

CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2– ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1.

Results

A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study.

Conclusions

Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2− ABC, including populations of interest (NCT02941926).

 

Mammographic breast density and the risk of breast cancer: A systematic review and meta-analysis

 

by F.T.H. Bodewes, A.A. van Asselt, M.D. Dorrius, M.J.W. Greuter, G.H. de Bock 

 

The Breast: Published: September 26, 2022

 

Objectives

Mammographic density is a well-defined risk factor for breast cancer and having extremely dense breast tissue is associated with a one-to six-fold increased risk of breast cancer. However, it is questioned whether this increased risk estimate is applicable to current breast density classification methods. Therefore, the aim of this study was to further investigate and clarify the association between mammographic density and breast cancer risk based on current literature.

Methods

Medline, Embase and Web of Science were systematically searched for articles published since 2013, that used BI-RADS lexicon 5th edition and incorporated data on digital mammography. Crude and maximally confounder-adjusted data were pooled in odds ratios (ORs) using random-effects models. Heterogeneity regarding breast cancer risks were investigated using I2 statistic, stratified and sensitivity analyses.

Results

Nine observational studies were included. Having extremely dense breast tissue (BI-RADS density D) resulted in a 2.11-fold (95% CI 1.84–2.42) increased breast cancer risk compared to having scattered dense breast tissue (BI-RADS density B). Sensitivity analysis showed that when only using data that had adjusted for age and BMI, the breast cancer risk was 1.83-fold (95% CI 1.52–2.21) increased. Both results were statistically significant and homogenous.

Conclusions

Mammographic breast density BI-RADS D is associated with an approximately two-fold increased risk of breast cancer compared to having BI-RADS density B in general population women. This is a novel and lower risk estimate compared to previously reported and might be explained due to the use of digital mammography and BI-RADS lexicon 5th edition.

 

 

Suggestion for the omission of post-mastectomy chest wall radiation therapy in patients who underwent skin-sparing/nipple-sparing mastectomy

 

by Nalee Kim, Won Park, Won Kyung Cho, Hae Young Kim, Doo Ho Choi, Seok Jin Nam, Seok Won Kim, Jeong Eon Lee, Jonghan Yu, Byung Joo Chae, Se Kyung Lee, Jai Min Ryu, Goo-Hyun Mun, Jai-Kyong Pyon, Byung-Joon Jeon 

 

The Breast: Published: September 23, 2022

 

Aim

Both skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) have been widely adopted. Although postmastectomy radiation therapy (PMRT) can improve clinical outcomes, it can worsen cosmesis following reconstruction. Therefore, identifying risk factors of ipsilateral breast tumor recurrence (IBTR) could help de-escalate PMRT after NSM/SSM in patients with pT1-2 disease.

Methods

We retrospectively reviewed patients treated with SSM (N = 400) and NSM (N = 156) in patients with pT1-2N0-1 disease between 2009 and 2016. Seventy-four patients received PMRT with 50–50.4 Gy in 25–28 fractions. The Cox proportional hazards model was used to analyze the prognostic factors of IBTR.

Results

With a median follow-up of 66.2 months, 17 IBTR events were observed, with 5-year IBTR-free rate of 97.2%. Although only one IBTR was observed after PMRT, there was no statistical difference in the 5-year IBTR-free rate (PMRT vs. no PMRT, 98.6% vs. 97.0%, p = 0.360). Multivariable analyses demonstrated that age ≤45 years and lymphovascular invasion (LVI) were adverse features of IBTR. The low-risk group (0 risk factor) showed a better 5-year IBTR-free rate than the high-risk group (≥1 risk factor) (100.0% vs. 95.8%, p = 0.003). In the high-risk group, PMRT slightly improved 5-year IBTR-free rate compared with no PMRT (98.6% vs. 95.2%, p = 0.166). In addition, PMRT increased 5-year cumulative incidence of reconstruction failure (10.0% vs. 2.8%, p = 0.001).

Conclusion

We identified risk factors (age and LVI) related to IBTR following upfront SSM/NSM with pT1-2 disease. As a hypothesis-generating study, de-escalation of PMRT by omitting chest wall irradiation in selective patients could improve reconstruction-related complications without compromising oncologic outcomes.

 

 

 

Association of Unilateral Latissimus Dorsi Muscle Harvest for Breast Reconstruction with Postoperative Spinal Posture

 

by Kim, Jisu; Lee, Hojune; Pyon, Jai-Kyong; Mun, Goo-Hyun; Bang, Sa Ik; Jeon, Byung-Joon; Lee, Kyeong-Tae 

 

Plastic and Reconstructive Surgery: September 2022 - Volume 150 - Issue 3 - p 644e-654e

 

Background: 

The latissimus dorsi muscle originates from the lower thoracic spine with broad attachment and plays a subsidiary role in spinal postural stability. The authors investigated whether harvesting unilateral latissimus dorsi muscle for breast reconstruction could influence spinal posture in the long term.

Methods: 

Patients who underwent immediate unilateral breast reconstruction between 2002 and 2010 were reviewed. They were grouped according to reconstruction methods: latissimus dorsi muscle flap and tissue expander/implant. The Cobb angle was assessed twice at each of five different time points (preoperatively and 2, 4, 6, and 8 years postoperatively) by an independent physician blinded to the reconstruction modality. Postoperative scoliosis was defined as a mean Cobb angle greater than 10 degrees at 8 years postoperatively. The trends of changes in Cobb angle over time and the rates of postoperative scoliosis were compared between reconstruction methods.

Results: 

In total, 153 women were analyzed, including 102 using latissimus dorsi muscle flap and 51 using tissue expander/implant, with a median follow-up of 103 months. The latissimus dorsi flap group showed enhanced trends of increasing postoperative Cobb angles as compared with the tissue expander/implant group, and the difference remained significant after adjusting for other variables (p = 0.001). The rate of postoperative scoliosis was significantly higher in the latissimus dorsi flap group than in the control group (p = 0.029). Multivariable analyses revealed that use of the latissimus dorsi flap was associated with a significantly increased rate of postoperative scoliosis.

Conclusion: 

Unilateral latissimus dorsi muscle flap harvest for breast reconstruction might be associated with changes in spinal posture in the long term.

 

Breast Surgery Bulletin: September 2022

 

Neoadjuvant therapy in triple-negative breast cancer: A systematic review and network meta-analysis

 

by Ying-Yi Lin, Hong-Fei Gao, Xin Yang, Teng Zhu, Xing-xing Zheng, Fei Ji, Liu-Lu Zhang, Ci-Qiu Yang, Mei Yang, Jie-Qing Li, Min-Yi Cheng, Kun Wang

The Breast: August 19, 2022

Background

Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established.

Methods

Literature search was conducted from inception to February 12, 2022. Phase 2 and 3 randomized controlled trials (RCTs) investigating neoadjuvant therapy for TNBC were eligible. The primary outcome was pathologic complete response (pCR); the secondary outcomes were all-cause treatment discontinuation, disease-free survival or event-free survival (DFS/EFS), and overall survival. Odd ratios (OR) with 95% credible intervals (CrI) were used to estimate binary outcomes; hazard ratios (HR) with 95% CrI were used to estimate time-to-event outcomes. Bayesian network meta-analysis was implemented for each endpoint. Sensitivity analysis and network meta-regression were done.

Results

41 RCTs (N = 7109 TNBC patients) were eligible. Compared with anthracycline- and taxane-based chemotherapy (ChT), PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with a significant increased pCR rate (OR 3.95; 95% CrI 1.81–9.44) and a higher risk of premature treatment discontinuation (3.25; 1.26–8.29). Compared with dose-dense anthracycline- and taxane-based ChT, the combined treatment was not associated with significantly improved pCR (OR 2.57; 95% CrI 0.69–9.92). In terms of time-to-event outcomes, PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with significantly improved DFS/EFS (HR 0.42; 95% CrI 0.19–0.81).

Conclusions

PD-1 inhibitor plus platinum and anthracycline- and taxane-based ChT was currently the most efficacious regimen for pCR and DFS/EFS improvement in TNBC. The choice of chemotherapy backbone, optimization of patient selection with close follow-up and proactive symptomatic managements are essential to the antitumor activity of PD-1 inhibitor.

 

Family history of breast cancer, mammographic breast density and breast cancer risk: Findings from a cohort study of Korean women

 

by Thi Xuan Mai Tran, Soyeoun Kim, Huiyeon Song, Boyoung Park 

 

The Breast: August 23, 2022

 

Background

This study investigated whether the association between family history of breast cancer in first-degree relatives and breast cancer risk varies by breast density.

Methods

Women aged 40 years and older who underwent screening between 2009 and 2010 were followed up until 2020. Family history was assessed using a self-reported questionnaire. Using Breast Imaging Reporting and Data System (BI-RADS), breast density was categorized into dense breast (heterogeneously or extremely dense) and non-dense breast (almost entirely fatty or scattered areas of fibro-glandular). Cox regression model was used to assess the association between family history and breast cancer risk.

Results

Of the 4,835,507 women, 79,153 (1.6%) reported having a family history of breast cancer and 77,238 women developed breast cancer. Family history led to an increase in the 5-year cumulative incidence in women with dense- and non-dense breasts. Results from the regression model with and without adjustment for breast density yielded similar HRs in all age groups, suggesting that breast density did not modify the association between family history and breast cancer. After adjusting for breast density and other factors, family history of breast cancer was associated with an increased risk of breast cancer in all three age groups (age 40–49 years: aHR 1.96, 95% confidence interval [CI] 1.85–2.08; age 50–64 years: aHR 1.70, 95% CI 1.58–1.82, and age ≥65 years: aHR 1.95, 95% CI 1.78–2.14).

Conclusion

Family history of breast cancer and breast density are independently associated with breast cancer. Both factors should be carefully considered in future risk prediction models of breast cancer.

 

Transverse Upper Gracilis Flap Breast Reconstruction: A 5-Year Consecutive Case Series of Patient-Reported Outcomes

 

by Jessica, Anne Savage; Zhao, Jade; Mackey, Simon; Blackburn, Adam Victor 

 

Plastic and Reconstructive Surgery: August 2022 - Volume 150 - Issue 2 - p 258-268

 

Background: 

The transverse upper gracilis flap is an important reconstructive option for patients who desire autologous reconstruction after mastectomy but in whom a deep inferior epigastric perforator flap is unavailable or undesirable. The authors present an analysis of outcomes and patient satisfaction results, from a consecutive series in a single institution.

Methods: 

Using a prospectively populated free flap database, all patients undergoing transverse upper gracilis flap breast reconstruction for a mastectomy defect between January of 2013 and December of 2017 were identified. Retrospective review of clinical notes, admissions, and discharge information was conducted to identify outcomes, secondary operations, and complications. All patients were contacted by letter and invited to take part in a patient satisfaction survey a minimum of 12 months after free-flap surgery.

Results: 

Seventy-eight patients underwent transverse upper gracilis flap breast reconstruction using a total of 103 transverse upper gracilis flaps to reconstruct 99 breast mounds in the 5-year period studied. Patient satisfaction is evidenced by BREAST-Q scores showing 81 ± 19 percent Satisfaction with Breasts, 80 ± 20 percent Psychosocial Well-Being, and 84 ± 19 percent Physical Well-Being of the chest. Forty-six of 53 (87 percent) report satisfaction with the postoperative appearance of their thigh unclothed and 51 of 53 (96 percent) report satisfaction clothed.

Conclusions: 

This is the first consecutive series of transverse upper gracilis flap breast reconstruction outcomes that presents BREAST-Q scores for multiple, postoperative reconstruction modules and details complications stratified by Clavien-Dindo score. The methodology can be easily replicated and benchmarked against. Our donor-site complication rates are lower than previous publications and patient satisfaction data reveal that this is a well-accepted option for patients.

 

 

 

 

Microneedling Outcomes in Early Postsurgical Scars

 

by Claytor, R. Brannon; Sheck, Casey Gene; Chopra, Vinod 

 

Plastic and Reconstructive Surgery: September 2022 - Volume 150 - Issue 3 - p 557e-561e

 

Background: 

Scars are a vexing sequela of surgery. Microneedling, also known as minimally invasive percutaneous collagen induction, has demonstrated impressive improvements in chronic acne scars; however, no evidence exists for treating postsurgical scars during active wound healing. The purpose of this study was to demonstrate the utility and safe use of minimally invasive percutaneous collagen induction in acute postsurgical scars.

Methods: 

Twenty-five patients who underwent surgery had scars treated with three treatments of minimally invasive percutaneous collagen induction in the postoperative period. Scar assessment was measured by Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, and Global Aesthetic Improvement Scale after each of the three treatments and at final 2-month follow-up.

Results: 

Patients had positive improvement in Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, and Global Aesthetic Improvement Scale scores at 16-week posttreatment initiation evaluation compared to initial measurement (p < 0.001). No statistically significant differences were noted when comparing the age of the patient, location of scars, or Fitzpatrick phototype scales among patients. When comparing patients who began treatment early (6 to 7 weeks postoperatively) to those who began treatment late (13 to 16 weeks postoperatively), there was a statistically significant difference in the Patient and Observer Scar Assessment Scale group (p < 0.04).

Conclusions: 

Postsurgical scars treated with minimally invasive percutaneous collagen induction in the maturation and remodeling phase had no adverse outcomes. Interestingly, the data show treatment initiated early in the maturation phase (6 to 7 weeks postoperatively), while natural collagen formation was tapering off, demonstrated improved aesthetic outcomes compared to treatments initiated late in the maturation phase (13 to 16 weeks postoperatively).

 

 

 

 

 

Nomogram for predicting overall survival in patients with triple-negative apocrine breast cancer: Surveillance, epidemiology, and end results-based analysis

 

by Yinggang Xu, Weiwei Zhang, Jinzhi He, Ye Wang, Rui Chen, Wenjie Shi, Xinyu Wan, Xiaoqing Shi, Xiaofeng Huang, Jue Wang, Xiaoming Zha 

 

The Breast: September 01, 2022

 

Purpose

Triple-negative apocrine carcinoma (TNAC) is a sort of triple-negative breast cancer (TNBC) that is rare and prognosis of these patients is unclear. The present study constructed an effective nomogram to assist in predicting TNAC patients overall survival (OS).

Methods

A total of 373 TNAC patients from the surveillance, epidemiology, and end results (SEER) got extracted from 2010 to 2016 and were divided into training (n = 261) and external validation (n = 112) groups (split ratio, 7:3) randomly. A Cox regression model was utilized to creating a nomogram according to the risk factors affecting prognosis. The predictive capability of the nomogram was estimated with receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

Results

Multivariate Cox regression analysis revealed age, surgery, chemotherapy, stage, and first malignant primary as independent predictors of OS. A prediction model was constructed and virtualized using the nomogram. The time-dependent area under the curve (AUC) showed satisfactory discrimination of the nomogram. Good consistency was shown on the calibration curves in OS between actual observations and the nomogram prediction. What's more, DCA showed that the nomogram had incredible clinical utility. Through separating the patients into groups of low and high risk group that connects with the risk system that shows a huge difference between the low-risk and high risk OS (P < 0.001).

Conclusion

To predict the OS in TNAC patients, the nomogram utilizing the risk stratification system that is corresponding. These tools may help to evaluate patient prognosis and guide treatment decisions.

 

Current and future burden of breast cancer: Global statistics for 2020 and 2040

 

by Melina Arnold, Eileen Morgan, Harriet Rumgay, Allini Mafra, Deependra Singh, Mathieu Laversanne, Jerome Vignat, Julie R. Gralow, Fatima Cardoso, Sabine Siesling, Isabelle Soerjomataram 

 

The Breast: September 01, 2022

 

Background

Breast cancer is the most commonly diagnosed cancer worldwide, and its burden has been rising over the past decades. In this article, we examine and describe the global burden of breast cancer in 2020 and predictions for the year 2040.

Methods

Estimates of new female breast cancer cases and deaths in 2020 were abstracted from the GLOBOCAN database. Age-standardized incidence and mortality rates were calculated per 100,000 females by country, world region, and level of human development. Predicted cases and deaths were computed based on global demographic projections for the year 2040.

Results

Over 2.3 million new cases and 685,000 deaths from breast cancer occurred in 2020. Large geographic variation across countries and world regions exists, with incidence rates ranging from <40 per 100,000 females in some Asian and African countries, to over 80 per 100,000 in Australia/New Zealand, Northern America, and parts of Europe. Smaller geographical variation was observed for mortality; however, transitioning countries continue to carry a disproportionate share of breast cancer deaths relative to transitioned countries. By 2040, the burden from breast cancer is predicted to increase to over 3 million new cases and 1 million deaths every year because of population growth and ageing alone.

Conclusion

Breast cancer is the most common cancer worldwide and continues to have a large impact on the global number of cancer deaths. Global efforts are needed to counteract its growing burden, especially in transitioning countries where incidence is rising rapidly, and mortality rates remain high.

 

A systematic review and meta-analysis of BRCA1/2 mutation for predicting the effect of platinum-based chemotherapy in triple-negative breast cancer

 

by Xiaomeng Jia, Kainan Wang, Lingzhi Xu, Ning Li, Zuowei Zhao, Man Li 

 

The Breast: September 02, 2022

Introduction

Platinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.

Materials and methods

All studies applying PBC with a subgroup of BRCA1/2 status were included. All endpoints, including pCR and RCB in the neoadjuvant phase, DFS in the adjuvant phase, ORR, PFS, and OS in the advanced phase, were assessed using HRs and 95% Cl.

Results

From the 22 studies included, there were 2158 patients with TNBC, with 392 (18%) bearing the BRCA1/2 gene mutation. Based on 13 studies applying neoadjuvant PBC, we discovered that BRCA1/2 mutation was substantially associated with a 17.6% increased pCR rate (HR 1.32, 95% CI 1.17–1.49, p < 0.00001; I2 = 51%). Same result was observed in RCB0/I index (HR 1.38, 95% CI 1.08–1.76, P = 0.009; I2 = 0%). The meta-analysis of 6 trials addressing advanced therapy revealed that ORR rates were significantly higher in patients with BRCA1/2 mutation (HR 1.91, 95% CI 1.48–2.47, p < 0.00001; I2 = 32%), as well as PFS(HR 1.13, 95% CI 0.81–1.57, P = 0.47; I2 = 0%) and OS (HR 1.89, 95% CI 1.22–2.92, P = 0.004; I2 = 0%).

Conclusion

According to our meta-analysis of 22 trials in TNBC, BRCA1/2 mutation carriers were significantly more sensitive to PBC regimens, especially in neoadjuvant and advanced therapy.

 

Treatment and survival outcomes in older women with primary breast cancer: A retrospective propensity score-matched analysis

 

by Yuting Sang, Benlong Yang, Miao Mo, Shiyang Liu, Xujie Zhou, Jiajian Chen, Shuang Hao, Xiaoyan Huang, Guangyu Liu, Zhimin Shao, Jiong Wu 

 

The Breast: September 06, 2022

 

Purpose

Changes in biological features and functional status make management decisions in older women with primary breast cancer complicated. We aimed to provide an overview of the clinicopathological characteristics and survival outcomes of older breast cancer patients based on the current treatment strategies.

Methods

Female patients diagnosed with primary invasive breast cancer at Fudan University Shanghai Cancer Centre from 2008 to 2016 were included. Patients were divided into a younger group (<65 years) and older group (≥65 years). Propensity score matching was utilised to generate balanced cohorts.

Results

A total of 13,707 patients met the study criteria. Compared with younger patients, older patients had a higher Charlson Comorbidity Index (p < 0.001), less lymph node metastasis (p = 0.009), more advanced tumour stage (p = 0.038), and a larger proportion of estrogen receptor-positive (p < 0.001) and epidermal growth factor receptor 2-negative (p < 0.001) tumours. Older patients were likely to receive mastectomy and axillary lymph node dissection in addition to a lower proportion of adjuvant chemotherapy. Adjuvant chemotherapy (HR [hazard ratio] 0.69, p = 0.039) was independently correlated with better overall survival in the older patients. This survival benefit (HR 0.58, p = 0.041) was confirmed in matched cohorts. Among the older patients with larger tumours (HR 0.48, p = 0.038) and more lymph node involvement (HR 0.44, p = 0.040), adjuvant chemotherapy was associated with a significant survival benefit.

Conclusion

Older breast cancer patients showed less aggressive biological characteristics, intensive surgical and moderate medical preferences. The addition of adjuvant chemotherapy should be considered for older patients, especially for patients with large tumours and more lymph node involvement.

 

Does the 21-gene recurrence score have clinical utility in HR+/HER2+ breast cancer?

by Nadeem Bilani, Fionnuala Crowley, Mohammad Mohanna, Mira Itani, Marita Yaghi, Diana Saravia, Iktej Jabbal, Barbara Dominguez, Hong Liang, Zeina Nahleh 

 

The Breast: September 06, 2022

The 21-gene recurrence score assay has been validated as a predictive biomarker in early-stage HR+ and HER2-breast cancer. It is not indicated for use in HER2+ disease based on national guidelines. In this study, we assessed the value of 21-gene recurrence score, or OncotypeDX (ODX), testing in HR+/HER2+ breast cancer.

We used the National Cancer Database to identify patients with stages I-II, HR+/HER2+ breast cancer who received multi-gene testing with ODX. We the explored the prognostic and predictive value of this biomarker through various forms of survival modeling.

ODX testing was performed in n = 5,280 patients. N = 2,678 patients (50.7%) had a RS < 26, while n = 2,602 (49.3%) had a RS≥26. In Kaplan-Meier survival modeling for patients with recurrence scores <26, there was no significant difference in overall survival (p = 0.445) between patients receiving different systemic treatment regimens. However, when recurrence scores were ≥26, there was a statistically-significant difference in overall survival between systemic treatment regimens (p < 0.001). 5-year overall survival was highest (97.4%) for patients receiving triple therapy (anti-HER2 with chemotherapy and endocrine therapy), followed by those receiving dual therapy with endocrine and anti-HER2 (96.7%), and endocrine with chemotherapy (94.9%). Patients receiving endocrine therapy alone exhibited the lowest 5-year overall survival (88.5%).

Results

from this large national cancer registry suggest that multigene testing may have predictive value in treatment selection of patients with early-stage, HR+/HER2+ breast cancer. Prospective trials are warranted to identify subgroups of patients with HR+/HER2+ breast cancer who can be spared anti-HER2 treatments and cytotoxic chemotherapy.

 

 

Prognosis stratification and postoperative radiation therapy utilization in adenoid cystic carcinoma of the breast

by Di Zhang, Lixi Li, Fei Ma 

The Breast: September 10, 2022

Purpose

Adenoid cystic carcinoma of the breast (ACCB) is a rare malignancy with a favorable prognosis. Little information exists regarding the impact of postoperative radiation therapy (RT) on survival outcome in patients with ACCB. This study aimed to evaluate the clinical significance of postoperative RT in ACCB.

Methods

Data of patients with ACCB were extracted from the Surveillance, Epidemiology, and End Results database (2000–2019). Univariate and multivariable Cox regression analyses were performed to identify prognostic factors. In addition, a nomogram model was constructed and internally validated for discrimination and calibration. The value of postoperative RT was respectively accessed in each risk subgroup according to nomogram-deduced individualized score.

Results

A total of 689 eligible patients were included in the analysis. Partial mastectomy was associated with an increased risk of death compared with partial mastectomy plus postoperative RT (P = 0.020), but total mastectomy with or without postoperative RT was comparable (P = 0.624). Then, in-depth analysis was performed for patients receiving breast-conversing therapy (n = 485, the training set vs. the testing set = 340 vs. 145). Age at diagnosis, histological grade, and T stage were identified as prognostic factors for overall survival (OS) (All P < 0.05). A nomogram was constructed to provide predictive accuracy toward individual OS rates of ACCB and to divide patients into different risk subgroups. Notably, compared with non-RT, postoperative RT significantly improved OS in the high-risk subgroup (P = 0.006 for the training set, and P = 0.013 for the overall population) but not in the low-risk subgroup (P = 0.807 for the training set, and P = 0.293 for the overall population), suggesting that these patients may be able to exempt from postoperative RT.

Conclusion

A robust and effective nomogram was developed to predict prognosis and assist in treatment decisions in patients with ACCB undergoing partial mastectomy.

 

 

 

 

Defining the Relationship between Pocket and Breast Implant Surface Area as the Basis for a New Classification System for Capsular Contracture

 

by Hammond, Dennis C.; Chaudhry, Arif 

 

Plastic and Reconstructive Surgery: September 2022 - Volume 150 - Issue 3 - p 496-509

 

Background: 

The precise cause of and treatment for capsular contracture remains uncertain, at least partially because there is no reliable quantitative measurement tool. To address this, it is postulated that the surface area of an implant as defined by the surrounding pocket may provide a quantifiable variable that can be measured to evaluate the degree of capsular contracture.

Methods: 

A bench model for capsular contracture was developed. The surface area of a series of spherical test objects and noncontracted and contracted breast implants was measured using a wax-coating technique and three-dimensional reconstructions created from computed tomographic scan images.

Results: 

Comparison of the mathematically calculated surface areas to the wax and computed tomographic scan results for spheres of known dimension provided nearly identical values, documenting the accuracy of the two experimental methods. Comparison of the surface area measurements between the test groups showed that the average decrease in surface area for all implants was 20 percent, ranging from a high of 30.9 percent for a low-profile implant to a low of 14.1 percent for a high-profile implant. The anatomically shaped devices demonstrated nearly uniform degrees of surface area change over three different heights with volume and projection held relatively constant.

Conclusions: 

The described bench model provides a useful tool for the study of capsular contracture. Surface area is a descriptive variable that can assess the degree of capsular contracture that is present. A classification system based on surface area is presented.

 

 

 

The Batwing Mastopexy in Immediate Implant-Based Breast Reconstruction: An Aesthetic Enhancement for Patients with Cancer

 

by Kadakia, Nikita; Kubiak, Jeremy W.; Landau, Mark J.; Mohiuddin, Waseem; Lewis, Priya G.; Kim, Hahns Y. 

 

Plastic and Reconstructive Surgery: September 2022 - Volume 150 - Issue 3 - p 487-495

 

Background: 

Historically, many patients with breast ptosis have been excluded from nipple-sparing mastectomies. By performing mastopexy at the time of immediate reconstruction, more patients with breast ptosis can be considered for nipple-sparing mastectomies. The authors review their experience of simultaneous batwing mastopexy performed at the time of immediate implant-based reconstruction.

Methods: 

Using retrospective chart review, the authors identified patients who underwent immediate implant-based breast reconstruction from 2015 through 2020 at a single institution. The patients were divided into two cohorts—batwing mastopexy and standard reconstruction (no mastopexy)—and compared.

Results: 

A total of 324 breast operations in 188 patients were included (80 concurrent batwing and 244 standard implant-based reconstructions). Patient characteristics were similar between the groups, except that patients in the batwing group had greater ptosis and more patients in the standard group underwent adjuvant chemotherapy. Mean follow-up was 15.9 months (range, 3.19 to 55.20 months). Complication rates were comparable in the batwing and standard groups, with no statistically significant differences in rates of hematoma (1.3 versus 3.3 percent; = 0.34), seroma (5.0 versus 8.2 percent; p = 0.34), major infection (8.8 versus 9.0 percent; p = 0.94), skin or nipple necrosis (6.3 versus 11.5 percent; p = 0.18), or explantation (11.3 versus 14.8 percent; p = 0.43). The rate of minor infections was higher in the group with concurrent batwing mastopexy (10.0 versus 3.7 percent; p = 0.03).

Conclusions: 

The authors demonstrate that simultaneous batwing mastopexy can be performed safely at the time of immediate breast reconstruction. This technique provides comparable complication rates, improves aesthetic outcomes in patients with significant ptosis or macromastia, and allows nipple-sparing mastectomy to be an option for those who would otherwise be excluded.

 

Breast Surgery Bulletin: July 2022

 

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer

 

by A. Viansone, B. Pellegrino, C. Omarini, M. Pistelli, D. Boggiani, A. Sikokis, V. Uliana, D. Zanoni, C. Tommasi, B. Bortesi, F. Bonatti, F. Piacentini, L. Cortesi, R. Camisa, P. Sgargi, M. Michiara, A. Musolino 

 

The Breast: Published: July 31, 2022

 

Background

HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients.

Materials and methods

Using a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status.

Results

One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7).

Conclusions

Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.