Breast Surgery Bulletin - March 2022

 

Local treatment options for young women with ductal carcinoma in situ: A systematic review and meta-analysis comparing breast conserving surgery with or without adjuvant radiotherapy, and mastectomy

 

by Ju-Chun Chien, Wen-Shan Liu, Wei-Tzu Huang, Liang-Chung Shih, Wen-Chung Liu, Yu-Chia Chen, Kang-Ju Chou, Yow-Ling Shiue, Pei-Chin Lin 

 

The Breast: VOLUME 63, P29-36, JUNE 01, 2022

 

 

Purpose

Young age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women.

Methods

PubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest.

Results

We included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50–0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98–1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06–9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes.

Conclusion

This study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.

 

 

Efficacy of trastuzumab emtansine (T-DM1) and lapatinib after dual HER2 inhibition with trastuzumab and pertuzumab in patient with metastatic breast cancer: Retrospective data from a French multicenter real-life cohort

by Fabien Moinard-Butot, Caroline Saint-Martin, Carole Pflumio, Matthieu Carton, William Jacot, Paul-Henri Cottu, Véronique Diéras, Florence Dalenc, Anthony Goncalves, Marc Debled, Anne Patsouris, Marie-Ange Mouret-Reynier, Laurence Vanlemmens, Marianne Leheurteur, George Emile, Jean-Marc Ferrero, Isabelle Desmoulins, Lionel Uwer, Jean-Christophe Eymard, Bianca Cheaib, Coralie Courtinard, Thomas Bachelot, Michaël Chevrot, Thierry Petit 

The Breast: VOLUME 63, P54-60, JUNE 01, 2022

 

Purpose

Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies.

Methods

ESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine.

Results

Cohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS.

Conclusion

First-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine.

 

 

Clinical characteristics and survival outcome of patients with estrogen receptor low positive breast cancer

 

by Chuanxu Luo, Xiaorong Zhong, Yu Fan, Yanqi Wu, Hong Zheng, Ting Luo 

 

The Breast:  VOLUME 63, P24-28, JUNE 01, 2022

 

Background

The benefit of endocrine therapy for patients with estrogen receptor (ER)-low (1%–10%) positive breast cancer is a matter for debate. We aimed to compare the clinical characteristics and survival outcome of ER-low patients with ER-high (＞10%) positive patients and ER-negative patients.

Methods

From the breast cancer database of our institution, we identified 5466 patients with known ER status who were diagnosed with early-stage breast cancer between January 2008 and December 2016. Variables associated with initiation of endocrine therapy were identified using multivariate logistic regression model. According to ER status, all patients were classified into ER-low (1%–10%), ER-high (>10%) and ER-negative subgroups. Fine and Gray competing risks regression was performed to compare the survival outcome of three subgroups.

Results

Age at diagnosis, ER status and progesterone receptor (PR) status were identified as correlates of initiation of endocrine therapy. ER-low patients were more likely to have advanced, PR-negative, human epidermal growth factor receptor 2 (HER2)-positive or grade Ⅲ disease compared to ER-high patients. Similar to ER-negative patients, ER-low patients presented increased rate of locoregional recurrence (LRR), distant recurrence (DR) and breast cancer mortality (BCM) than ER-high patients. Endocrine therapy showed nonsignificant trends toward lower LRR, DR and BCM in ER-low patients.

Conclusion

Similar to ER-negative patients, ER-low patients had more aggressive clinical characteristics and worse survival outcome than ER-high patients. ER-low patients appeared to benefit less from endocrine therapy. Randomized studies are needed to further explore the endocrine responsiveness of ER-low patients.

 

 

Comparing Outcomes after Oncoplastic Breast Reduction and Breast Reduction for Benign Macromastia

 

by Marano, Andrew A.; Grover, Karan; Peysakhovich, Anya; Lin, Alexandra J.; Castillo, Wendy; Rohde, Christine H

 

Plastic and Reconstructive Surgery: March 2022 - Volume 149 - Issue 3 - p 541-548

 

Background: Oncoplastic breast reconstruction improves cosmetic outcomes when compared to standard breast conservation therapy alone. The authors studied whether tailoring a breast reduction to a cancer resection affects complication rates by comparing (1) outcomes between oncoplastic and benign macromastia patients and (2) complication rates between the cancer side and the symmetrizing side of an oncoplastic reduction.

Methods: A retrospective chart review was performed on female patients who underwent either oncoplastic or benign breast reduction over 9 years by a single surgeon. Patient demographics, intraoperative data, and postoperative outcomes were gathered from the electronic medical record. Chi-square and t tests were performed when appropriate to determine significance.

Results: Of the 211 patients included in the study, 62 (29.4 percent) underwent oncoplastic breast reduction and 149 (70.6 percent) underwent breast reduction for benign macromastia. Total resection weight was greater in the benign group (p = 0.00). There was a higher rate of loss of nipple sensation in the oncoplastic group (p = 0.005) but no differences in any other complication. There was a higher complication rate in the oncologic breast when compared to the symmetrizing breast within the oncoplastic cohort (p = 0.039), but no differences in the rates of individual complications.

Conclusions: Although the loss of nipple sensation was increased in patients undergoing oncoplastic breast reduction, all other outcomes were not significantly different between the two groups. The authors’ findings indicate that oncoplastic breast reduction can be performed with a safety profile similar to that of a standard breast reduction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

 

Impact of Incision Placement on Ischemic Complications in Microsurgical Breast Reconstruction

 

by Tevlin, Ruth; Griffin, Michelle; Karin, Mardi; Wapnir, Irene; Momeni, Arash 

Plastic and Reconstructive Surgery: February 2022 - Volume 149 - Issue 2 - p 316-322

Background: Nipple-sparing mastectomy is associated with greater patient satisfaction than non–nipple-sparing approaches. Although various nipple-sparing mastectomy incisions have been described, the authors hypothesized that incision location would impact the rate and location of ischemic complications to the mastectomy skin flap.

Methods: A prospectively maintained database was queried to identify patients who underwent nipple-sparing mastectomy with immediate microsurgical reconstruction with a minimum postoperative follow-up of 12 months. The impact of incision location on postoperative ischemic complications was investigated. Major complications were defined as those that required reexploration in the operating room or inpatient management; minor complications were amenable to outpatient management. Multivariable logistic and linear regression were performed to investigate risk factors for postoperative complications following breast reconstruction.

Results: Eighty-seven patients met inclusion criteria. The following nipple-sparing mastectomy incisions were used: radial with a periareolar extension (39 percent), inframammary fold (31 percent), vertical with a periareolar extension (22 percent), vertical (6 percent), and radial (2 percent). Seven patients (8 percent) had major complications, whereas twenty-six patients (29.9 percent) developed minor postoperative complications. Inframammary fold incisions were associated with significantly greater rates of mastectomy skin flap necrosis (p = 0.002), whereas periareolar incisions were associated with significantly greater rates of postoperative nipple-areola complex necrosis (p = 0.04).

Conclusions: The authors report a significant association between incision location and ischemic complications to the breast skin envelope in microsurgical breast reconstruction. The authors observed a significant association of inframammary fold and periareolar incisions with mastectomy skin flap and nipple-areola complex necrosis, respectively. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

 

Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial

by Matilda Appelgren, Helena Sackey, Yvonne Wengström, Karin Johansson, Johan Ahlgren, Yvette Andersson, Leif Bergkvist, Jan Frisell, Dan Lundstedt, Lisa Rydén, Malin Sund, Sara Alkner, Birgitte Vrou Offersen, Tove Filtenborg Tvedskov, Peer Christiansen, Jana de Boniface, the SENOMAC Trialists' Group 

The Breast: VOLUME 63, P16-23, JUNE 01, 2022

Introduction

This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection (ALND).

Methods

The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1–2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQ-C30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.

Results

Overall, 976 questionnaires (501 in the SLN biopsy only group and 475 in the completion ALND group) were analysed, corresponding to a response rate of 82.6%. No significant group differences in overall HRQoL were identified. Participants receiving SLN biopsy only, reported significantly lower symptom scores on the EORTC subscales of pain, arm symptoms and breast symptoms. The Lymph-ICF domain scores of physical function, mental function and mobility activities were significantly in favour of the SLN biopsy only group.

Conclusion

One year after surgery, arm morbidity is significantly worse affected by ALND than by SLN biopsy only. The results underline the importance of ongoing attempts to safely de-escalate axillary surgery.

 

Trends in axillary surgery and clinical outcomes among breast cancer patients with sentinel node metastasis

 

by Zongchao Gou, Xunxi Lu, Mengting He, Luoting Yu 

 

The Breast: VOLUME 63, P9-15, JUNE 01, 2022

 

Background

There is a lack of studies examining the long-term trend and survival of axillary surgery for breast cancer patients with sentinel node metastasis, especially for the patients with 3–5 node metastases.

Methods

Breast cancer patients with 1–5 sentinel node metastases from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. Our study presented the trend of axillary surgery and assessed the long-term survival of sentinel lymph node biopsy (SLNB) alone vs axillary lymph node dissection (ALND) for those patients.

Results

Of the 41,996 patients diagnosed with T1-2 breast cancer after lumpectomy and radiation included, 34,940 had 1-2 sentinel node metastases and 7056 had 3-5 sentinel node metastases. The percentage of patients undergoing SLNB alone increased from 22.4% in 2000 to 81.0% in 2016 for patients with 1–2 sentinel node metastases, and quadrupled from 5.2% in 2009 to 20.6% in 2016 for those with 3–5 sentinel node metastases. Completion of ALND did not benefit the long-term survival of 1–2 sentinel node metastasis patients (hazard ratio [HR] = 1.02, P = 0.539), but improved the long-term survival of 3–5 node metastasis patients (HR = 0.73, P < 0.001). Subgroup analysis demonstrated the inferiority of SLNB to ALND in all subgroups of 3–5 sentinel node metastases.

Conclusion

For patients with T1-2 breast cancer after lumpectomy and radiation, SLNB alone was an efficient and safe surgical choice for 1–2 sentinel node metastases but not for 3–5 sentinel node metastases. It is worth noting that for patients with 3–5 node metastasis, the proportion of omitted ALND quadrupled after 2009.

 

Microvascular Breast Reconstruction in the Era of Value-Based Care: Use of a Cosurgeon Is Associated with Reduced Costs, Improved Outcomes, and Added Value

 

by Mericli, Alexander F.; Chu, Carrie K.; Sisk, Geoffroy C.; Largo, Rene D.; Schaverien, Mark V.; Liu, Jun; Villa, Mark T.; Garvey, Patrick B. 

 

Plastic and Reconstructive Surgery: February 2022 - Volume 149 - Issue 2 - p 338-348

 

Background: Reducing complications while controlling costs is a central tenet of value-based health care. Bilateral microvascular breast reconstruction is a long operation with a relatively high complication rate. Using a two-surgeon team has been shown to improve safety in bilateral microvascular breast reconstruction; however, its impact on cost and efficiency has not been robustly studied. The authors hypothesized that a cosurgeon for bilateral microvascular breast reconstruction is safe, effective, and associated with reduced costs.

Methods: The authors retrospectively reviewed all patients who underwent bilateral microvascular breast reconstruction with either a single surgeon or surgeon/cosurgeon team over an 18-month period. Charges were converted to costs using the authors’ institutional cost-to-charge ratio. Surgeon opportunity costs were estimated using time-driven activity-based costing. Propensity scoring controlled for baseline characteristics between the two groups. A locally weighted logistic regression model analyzed the cosurgeon’s impact on outcomes and costs.

Results: The authors included 150 bilateral microvascular breast reconstructions (60 single-surgeon and 90 surgeon/cosurgeon reconstructions) with a median follow-up of 15 months. After matching, the presence of a cosurgeon was associated with a significantly reduced mean operative duration (change in operative duration, −107 minutes; p < 0.001) and cost (change in total cost, −$1101.50; p < 0.001), which was even more pronounced when surgeon/cosurgeon teams worked together frequently (change in operative duration, −132 minutes; change in total cost, −$1389; p = 0.007). The weighted logistic regression models identified that a cosurgeon was protective against breast-site complications and trended toward reduced overall and major complication rates.

Conclusion: The practice of using a of cosurgeon appears to be associated with reduced costs and improved outcomes, thereby potentially adding value to bilateral microvascular breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

 

Exploring breast surgeons’ reasons for women not undergoing immediate breast reconstruction

by Ashlee Matkin, Jennifer Redwood, Carmen Webb, Claire Temple-Oberle 

The Breast: VOLUME 63, P37-45, JUNE 01, 2022

Introduction

Factors influencing breast reconstruction rates in Canada are complex and multi-factorial, ranging from patient-related to systemic considerations. For plastic surgeons, rates of immediate breast reconstruction (IBR) hinge on referral patterns from general surgeons performing breast cancer surgery and informed discussions with patients about their goals and risk tolerance. We seek to understand the reasons Alberta patients are not receiving IBR as reported by general surgeons.

Methods

The Synoptec™ database is a synoptic operative report designed by Cancer Surgery Alberta™ and utilized by 95% of Alberta breast cancer surgeons. Within this report are mandatory questions regarding if a patient is receiving IBR and, if not, why. A retrospective review of this database was performed for all patients undergoing surgical treatment of breast cancer over two years. All statistical comparisons were made using chi-squared test for categorical variables with a p-value of 0.05 considered significant.

Results

Of 6253 patients undergoing breast cancer surgery, 2649 underwent mastectomy and 615 mastectomy patients received IBR. The most commonly reported reasons patients did not undergo IBR were patient preference (55%), high likelihood of postoperative radiation therapy (20%), and high risk due to patient co-morbidities (12%). Resource limitations (2%) and a lack of an IBR discussion (3%) was rarely cited as reasons for no IBR.

Conclusions

There are many reconstructive options following mastectomy in breast cancer survivors. This study provides a unique look into general surgeon reported reasons patients are not receiving IBR and demonstrates the need for further probing into the thought-process behind these reported reasons from both a surgeon and patient perspective.

 

A retrospective validation of CanAssist Breast in European early-stage breast cancer patient cohort

 

by Aparna Gunda, Chetana Basavaraj, Chandra Prakash Sv, Manjula Adinarayan, Ramu Kolli, Mallikarjuna Se, Cristina Saura, Fiorella Ruiz, Patricia Gomez, Vicente Peg, Jose Jimenez, Susanne Sprung, Heidi Fiegl, Christine Brunner, Daniel Egle, Bhattacharyya Gs, Manjiri Bakre 

 

The Breast: VOLUME 63, P1-8, JUNE 01, 2022

 

 CanAssist Breast (CAB), a prognostic test uses immunohistochemistry (IHC) approach coupled with artificial intelligence-based machine learning algorithm for prognosis of early-stage hormone-receptor positive, HER2/neu negative breast cancer patients. It was developed and validated in an Indian cohort. Here we report the first blinded validation of CAB in a multi-country European patient cohort. FFPE tumor samples from 864 patients were obtained from-Spain, Italy, Austria, and Germany. IHC was performed on these samples, followed by recurrence risk score prediction. The outcomes were obtained from medical records. The performance of CAB was analyzed by hazard ratios (HR) and Kaplan Meier curves. CAB stratified European cohort (n = 864) into distinct low- and high-risk groups for recurrence (P < 0.0001) with HR of 3.32 (1.85–5.93) like that of mixed (India, USA, and Europe) (n = 1974), 3.43 (2.34–4.93) and Indian cohort (n = 925), 3.09 (1.83–5.21). CAB provided significant prognostic information (P < 0.0001) in women aged ≤ 50 (HR: 4.42 (1.58–12.3), P < 0.0001) and >50 years (HR: 2.93 (1.44–5.96), P = 0.0002). CAB had an HR of 2.57 (1.26–5.26), P = 0.01) in women with N1 disease. CAB stratified significantly higher proportions (77%) as low-risk over IHC4 (55%) (P < 0.0001). Additionally, 82% of IHC4 intermediate-risk patients were stratified as low-risk by CAB. Accurate risk stratification of European patients by CAB coupled with its similar performance inIndian patients shows that CAB is robust and functions independent of ethnic differences. CAB can potentially prevent overtreatment in a greater number of patients compared to IHC4 demonstrating its usefulness for adjuvant systemic therapy planning in European breast cancer patients.

 

Essential amino acids deprivation is a potential strategy for breast cancer treatment

 

 

by Yajie Zhao, Chunrui Pu, Zhenzhen Liu 

 

The Breast: VOLUME 62, P152-161, APRIL 01, 2022

 

Aims

The study aimed to search novel, simple and practical index reflecting the level of essential amino acids (EAAs) metabolism in breast cancer (BC), as well as to explore the effect of enhanced EAAs metabolism on the prognosis and immune microenvironment of BC, thus providing new evidence for the application of EAAs deprivation in the BC treatment.

Methods

The study includes the analysis of multi-omics and clinical data of 13 BC cell lines and 2898 BC patients in the public database. Further validation was performed using multi-omics and immunohistochemistry data from 83 BC tissue samples collected at our hospital.

Results

According to the multi-omics data, the SLC7A5 to SLC7A8 Ratio (SSR) score was found to be significantly correlated with the EAAs level and EAAs-metabolic activity of BC, suggesting that the SSR score might be used as a biomarker to assess the degree of EAAs metabolism in BC. Besides, BC patients with high EAAs metabolism had shorter overall survival (OS) time, higher PD-L1 expression, and higher T regulatory cells (Tregs) infiltration, indicating that a high EAAs metabolism was related to a poor prognosis and immune suppression in BC. Additionally, MYC amplification is a critical molecular process in the metabolic reprogramming of EAAs in BC.

Conclusion

EAAs may be a possible therapeutic target for BC treatment.

 

Optimal Timing of Expander-to-Implant Exchange after Irradiation in Immediate Two-Stage Breast Reconstruction

 

 

by Kim, Ara; Bae, Juyoung; Bang, Sa-Ik; Pyon, Jai-Kyong 

 

Plastic and Reconstructive Surgery: February 2022 - Volume 149 - Issue 2 - p 185e-194e

 

Background: Time intervals for expander-to-implant exchange from radiation therapy have been reported to reduce device failure. This study investigated the optimal timing of expander-to-implant exchange after irradiation in terms of short- and long-term outcomes.

Methods: This retrospective review enrolled consecutive patients who underwent immediate two-stage breast reconstruction and radiation therapy to tissue expanders from 2010 to 2019. Receiver operating characteristic curves and the Youden index were used to estimate the optimal time from radiation therapy to implant placement in terms of 49-day (early) and 2-year (late) complications. Logistic regression analysis was performed to identify the risk factors for each complication.

Results: Of the 1675 patients, 133 were included. The 49-day and 2-year complication rates were 8.3 percent and 29.7 percent, respectively. Capsular contracture was the most common 2-year complication. The Youden index indicated that implant placement at 131 days after radiation therapy was most effective in reducing the 49-day complications, but that the 2-year complication was less significant, with lower sensitivity and area under the curve. Modified radical mastectomy, expander fill volume at radiation therapy, and size of permanent implant increased the odds of 49-day complications; none of them was associated with the odds of 2-year complications.

Conclusions: To reduce short-term complications, the best time point for permanent implant placement was 131 days after radiation therapy. However, there was no significant time interval for reducing long-term complications. Capsular contracture was an irreversible complication of radiation injury that was not modified by postirradiation variables including the time from irradiation or size of permanent implant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.