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.

 

Current challenges and unmet needs in treating patients with human epidermal growth factor receptor 2-positive advanced breast cancer

 

by Matti Aapro, Fatima Cardoso, Giuseppe Curigliano, Alexandru Eniu, Joseph Gligorov, Nadia Harbeck, Andreas Mueller, Olivia Pagani, Shani Paluch-Shimon, Elzbieta Senkus, Beat Thürlimann, Khalil Zaman 

 

The Breast: Published: July 30, 2022

 

Human epidermal growth factor receptor 2 oncogene (HER2-positive) overexpression/amplification occurs in less than 20% of breast cancers and has traditionally been associated with poor prognosis. Development of therapies that target HER2 has significantly improved outcomes for patients with HER2-positive advanced breast cancer (ABC). Currently available HER2-targeted agents include the monoclonal antibodies trastuzumab, pertuzumab, and margetuximab, the small-molecule inhibitors lapatinib, tucatinib, neratinib, and pyrotinib, as well as the antibody-drug conjugates trastuzumab emtansine and trastuzumab deruxtecan. Optimal sequencing of these agents in the continuum of the disease is critical to maximize treatment outcomes. The large body of clinical evidence generated over the past 2 decades aids clinicians in treatment decision-making. However, patients with HER2-positive ABC and specific disease characteristics and/or comorbidities, such as leptomeningeal disease, brain metastases, or cardiac dysfunction, are generally excluded from large randomized clinical trials, and elderly or frail patients are often underrepresented. In addition, there is great inequality in the accessibility of approved drugs across countries. This article addresses various challenging clinical situations when treating patients with HER2-positive ABC. The objective is to provide guidance to clinicians on how and when HER2-targeted therapies and additional treatments can be best implemented in routine clinical practice, on the basis of existing clinical evidence and expert opinion where needed.

 

The circulating tumor DNA (ctDNA) alteration level predicts therapeutic response in metastatic breast cancer: Novel prognostic indexes based on ctDNA

 

by Binliang Liu, Zheyu Hu, Jialu Ran, Ning Xie, Can Tian, Yu Tang, Quchang Ouyang 

 

The Breast: Published: July 19, 2022

 

Purpose

Circulating tumor DNA (ctDNA) has good clinical guiding value for metastatic breast cancer (MBC) patients. This study aimed to apply a novel genetic analysis approach for therapeutic prediction based on ctDNA alterations.

Method

This nonrandomized, multicenter study recruited 223 MBC patients (NCT05079074). Plasma samples were collected for target-capture deep sequencing of ctDNA at baseline, after the 2nd cycle of treatment, and when progressive disease (PD) was evaluated. Samples were categorized into four levels according to the number of ctDNA alterations: level 1 (no alterations), level 2 (1–2 alterations), level 3 (3–4 alterations) and level 4 (≥5 alterations). According to ctDNA alteration level and variant allele frequency (VAF), a novel ctDNA-level Response Evaluation Criterion in Solid Tumors (ctle-RECIST) was established to assess treatment response and predict progression-free survival (PFS).

Results

The median PFS in level 1 (6.63 months) patients was significantly longer than that in level 2–4 patients (level 2: 5.70 months; level 3–4: 4.90 months, p < 0.05). After 2 cycles of treatment, based on ctle-RECIST, the median PFS of level-based disease control rate (lev-DCR) patients was significantly longer than that of level-based PD (lev-PD) patients [HR 2.42 (1.52–3.85), p < 0.001]. In addition, we found that ctDNA level assessment could be a good supplement to radiologic assessment. The median PFS in the dual-DCR group tended to be longer than that in the single-DCR group [HR 1.41 (0.93–2.13), p = 0.107].

Conclusion

The ctDNA alteration level and ctle-RECIST could be novel biomarkers of prognosis and could complement radiologic assessment in MBC.

 

Dual-phase FDG PET/CT for predicting prognosis in operable breast cancer

 

by Haruka Ikejiri, Shinsuke Sasada, Akiko Emi, Norio Masumoto, Takayuki Kadoya, Morihito Okada 

The Breast: Published: July 19, 2022

 

Purpose

We aimed to investigate the role of dual-phase FDG PET/CT in predicting the prognosis of patients with operable breast cancer.

Methods

We retrospectively reviewed the data of 998 patients who underwent radical treatment for breast cancer. Before treatment, PET/CT scans were performed 1 and 2 h after FDG administration. The maximum standardized uptake value (SUVmax) at both time points (SUVmax1 and SUVmax2) in the primary tumor and the retention index (RI) were calculated. PET recurrence risk (PET-RR) was determined based on the SUVmax1 and RI, and disease-free survival (DFS) and overall survival (OS) were evaluated according to the metabolic parameters. Propensity score matching was performed to adjust for biological characteristics.

Results

The cut-off values for SUVmax1 and RI were 3 and 5%, respectively. The 5-year DFS was 94.9% and 86.1% (P < 0.001), and the 5-year OS was 97.6% and 92.7% (P < 0.001) in the low and high PET-RR groups, respectively. In multivariate analysis, high T status, nodal metastasis, the triple-negative subtype, and high PET-RR were independent factors of poor DFS. Propensity score matching revealed similar findings (5-year DFS 91.8% vs. 88.6%, P = 0.041 and 5-year OS 97.1% vs. 94.2%, P = 0.240, respectively).

Conclusion

The combined parameters of SUVmax1 and RI on dual-phase FDG PET/CT were useful for predicting prognosis of patients with breast cancer. Patients with a high SUVmax1 and a negative time course of FDG uptake had a favorable prognosis.

 

 

Simple oncoplastic breast defect closure improves long-term cosmetic outcome of breast conserving surgery for breast cancer: A randomised controlled trial

 

by Christopher Hadjittofi, Hend Almalki, Bahar Mirshekar-Syahkal, Simon Pain, Katalin Zechmeister, Maged Hussien 

 The Breast: Published: July 18, 2022

 

Introduction

Breast conserving surgery (BCS) is associated with unsatisfactory cosmetic outcomes in up to 30% of patients, carrying psychological and quality-of-life implications. This study compares long-term cosmetic outcomes after BCS for breast cancer with v without simple oncoplastic defect closure.

Methods

A randomised controlled trial was performed, recruiting patients who underwent BCS over four years and randomising to the “reshaping” group (closure of excision defect with mobilised breast tissue; n = 124) and to the “control” group (no attempt at defect closure; n = 109). The estimated excision volume (EEV) was <20% of breast volume (BV) in both groups. Photography and breast retraction assessment (BRA) were recorded preoperatively. Cosmetic outcomes were blindly assessed annually for five years by BRA, panel assessment of patients, and body image questionnaire (BIQ).

Results

There were no significant differences between the reshaping and control groups in mean age (52.4 v 53.0; p = 0.63), body mass index (27.8 v 27.7; p = 0.80), margin re-excision (9 v 9; p = 0.78), mean BV (562.5 v 590.3 cc; p = 0.56), mean EEV (54.6 v 60.1 cc; p = 0.14), mean EEV/BV ratio (11.2 v 11.0; p = 0.84), or mean specimen weight (52.1 v 57.7 g; p = 0.24). Reshaping group patients had significantly better outcomes compared to control group patients in terms of mean BRA (0.9 v 2.8; p < 0.0001), achieving a score of “good” or “excellent” by panel assessment at 5 years (75.8% v 48%, p < 0.0001), body image questionnaire top score at 5 years (66.9% v 35.8%; p = 0.0001).

Conclusions

Simple oncoplastic closure of defects after breast-conserving surgery improves long-term objective and subjective cosmetic outcomes.

 

Nerve Blocks in Breast Plastic Surgery: Outcomes, Complications, and Comparative Efficacy

 

by Abi-Rafeh, Jad; Safran, Tyler; Abi-Jaoude, Joanne; Kazan, Roy; Alabdulkarim, Abdulaziz; Davison, Peter G. 

Plastic and Reconstructive Surgery: July 2022 - Volume 150 - Issue 1 - p 1e-12e

Background:

As plastic surgeons continue to evaluate the utility of nonopioid analgesic alternatives, nerve block use in breast plastic surgery remains limited and unstandardized, with no syntheses of the available evidence to guide consensus on optimal approach.

Methods:

A systematic review was performed to evaluate the role of pectoralis nerve blocks, paravertebral nerve blocks, transversus abdominus plane blocks, and intercostal nerve blocks in flap-based breast reconstruction, prosthetic-based reconstruction, and aesthetic breast plastic surgery, independently.

Results:

Thirty-one articles reporting on a total of 2820 patients were included in the final analysis; 1500 patients (53 percent) received nerve blocks, and 1320 (47 percent) served as controls. Outcomes and complications were stratified according to procedures performed, blocks employed, techniques of administration, and anesthetic agents used. Overall, statistically significant reductions in opioid consumption were reported in 91 percent of studies evaluated, postoperative pain in 68 percent, postanesthesia care unit stay in 67 percent, postoperative nausea and vomiting in 53 percent, and duration of hospitalization in 50 percent. Nerve blocks did not significantly alter surgery and/or anesthesia time in 83 percent of studies assessed, whereas the overall, pooled complication rate was 1.6 percent.

Conclusions:

Transversus abdominus plane blocks provided excellent outcomes in autologous breast reconstruction, whereas both paravertebral nerve blocks and pectoralis nerve blocks demonstrated notable efficacy and versatility in an array of reconstructive and aesthetic procedures. Ultrasound guidance may minimize block-related complications, whereas the efficacy of adjunctive postoperative infusions was proven to be limited. As newer anesthetic agents and adjuvants continue to emerge, nerve blocks are set to represent essential components of the multimodal analgesic approach in breast plastic surgery.

 

 

Beauty Is in the Eye of the Beholder: Factors Influencing Disparity in Perceptions of Breast Reconstruction Aesthetic Outcomes

 

by Wu, Shannon S.; Duraes, Eliana F. R.; Scomacao, Isis; Morisada, Megan; Djohan, Risal S.; Bernard, Steven L.; Moreira, Andrea; Schwarz, Graham S.

 

Plastic and Reconstructive Surgery: July 2022 - Volume 150 - Issue 1 - p 42e-50e

 

Background:

Patient-reported outcomes are the primary measurement of breast reconstruction success, but results may be affected by nontechnical factors such as socioemotional determinants. Third-party observers provide an independent assessment of aesthetic outcomes. Factors associated with disparity between patient and observer perceptions of outcomes are not well understood.

Methods:

One hundred forty-seven patients underwent breast reconstruction at the authors’ institution between 2009 and 2011, completed the BREAST-Q, and had photographs graded by a diverse panel using the Validated Breast Aesthetic Scale. Patient satisfaction with breasts scores that aligned with observer scores were categorized as group 2; patient satisfaction that exceeded observer scores were group 1; and those lower than observer scores were group 3. Statistical analysis was performed using SPSS, with values of p < 0.05 considered statistically significant.

Results:

Twenty-eight patients (19 percent) were categorized as group 1, 93 (63 percent) in group 2, and 26 (18 percent) in group 3. Median overall appearance was highest in group 3 (median, 4.0; interquartile range, 4 to 4) and lowest in group 1 (median, 3.0; interquartile range, 2 to 3) (p < 0.001). Psychosocial, sexual, and physical well-being were significantly associated with disparity (group 1 or 3 status) (p < 0.01). Satisfaction with outcomes, nipples, abdomen, and breasts were significantly associated with disparity. Factors not significantly associated with disparity include age, body mass index, autologous or implant-based, adjuvant therapies, and timing of reconstruction.

Conclusions:

Incongruously high patient satisfaction with breast reconstruction aesthetics relative to third-party perception of aesthetic outcomes is associated with high quality-of-life scores. Incongruously low patient satisfaction with breast cosmesis compared with higher third-party perceptions was associated with low quality-of-life scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

 

Aesthetic Limitations in Direct-to-Implant Prepectoral Breast Reconstruction

 

By: Safran, Tyler; Al-Badarin, Faris; Al-Halabi, Becher; Viezel-Mathieu, Alex; Dionisopoulos, Tassos 

 

Plastic and Reconstructive Surgery: July 2022 - Volume 150 - Issue 1 - p 22e-31e

 

Background:

Prepectoral direct-to-implant reconstruction has become an alternative to staged subpectoral expander-based reconstruction. Although the surgical safety of this technique has been shown, aesthetic limitations have not been well-described. This article reports aesthetic limitations and elucidates risk factors that may predispose patients toward developing unfavorable outcomes following direct-to-implant prepectoral breast reconstruction.

Methods:

A retrospective chart review was performed, identifying patients who underwent prepectoral, direct-to-implant breast reconstruction from June of 2016 to June of 2019. Aesthetic limitations assessed included capsular contracture, rippling, implant malposition, and implant flipping.

Results:

Two hundred twenty-four consecutive women representing 334 breasts underwent immediate reconstruction performed by a single plastic surgeon. A midlateral incision was used in 185 breasts (55.4 percent) and the Wise pattern in 95 breasts (28.8 percent). The mean follow-up time was 30.5 months (45.3 to 18.3 months). Significant capsular contracture (grade 3 to 4) was noted in 27 breasts (8.1 percent), implant flipping in four breasts (1.2 percent), implant displacement in five breasts (1.5 percent), major rippling in nine breasts (2.7 percent), and minor rippling in 17 breasts (5.1 percent). The use of acellular dermal matrix had no significant effect on the aesthetic outcomes. In comparing breasts with postmastectomy radiation, there was a significant difference in the presence of minor rippling and capsular contracture (p < 0.05).

Conclusions:

This cohort represents the largest, single-surgeon, direct-to-implant prepectoral database in the literature. This report shows that aesthetic limitations were comparable to those seen with other forms of reconstruction. Complications did not differ in terms of acellular dermal matrix use. Certain factors can predispose patients to developing unfavorable aesthetic outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.