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.

 

Efficacy of neoadjuvant treatment with or without pertuzumab in patients with stage II and III HER2-positive breast cancer: A nationwide cohort analysis of pathologic response and 5-year survival

 

by Anna van der Voort, Marte C. Liefaard, Mette S. van Ramshorst, Erik van Werkhoven, Joyce Sanders, Jelle Wesseling, Astrid Scholten, Marie Jeanne Vrancken Peeters, Linda de Munck, Sabine Siesling, Gabe S. Sonke 

 

The Breast: Published: July 13, 2022

 

Background

Pathologic complete response (pCR) rates in early stage HER2-positive breast cancer improved after pertuzumab was added to neoadjuvant treatment. However, survival benefit is less-well established and seems mostly limited to node-positive patients. We used national cancer registry data to compare outcomes of patients treated with and without pertuzumab.

Methods

We identified stage II-III HER2-positive breast cancer patients treated with neoadjuvant trastuzumab-based chemotherapy between November 2013 until January 2016 from the Netherlands Cancer Registry. During that period pertuzumab was only available in the 37 hospitals that participated in the TRAIN-2 study. Missing grade and pCR-status were obtained from the Dutch Pathology Registry (PALGA) and cause of death from Statistics Netherlands. We used multiple imputation to impute missing data, multivariable logistic regression to evaluate the association between pertuzumab and pCR (ypT0/is, ypN0) and multivariable Cox regression models for overall survival and breast cancer specific survival (BCSS).

Results

We identified 1124 patients of whom 453 received pertuzumab. Baseline characteristics were comparable, although tumor grade was missing more often in patients treated without pertuzumab (12% vs. 2%). Pertuzumab improved pCR rates (41% vs 65%, adjusted odds ratio [aOR] 2.91; 95% CI:2.20–3.94). After a median follow-up of 6.0 years, 5-year BCSS rates were 95% and 98% respectively (adjusted hazard ratio [aHR]: 0.58; 95% CI:0.36–0.95). Younger patients derived more benefit from pertuzumab, but no other significant interactions were found.

Conclusion

These results support earlier data of a small survival benefit with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy which is most meaningful in younger patients.