Breast Surgery Bulletin: August 2021

 

Breast cancer screening using synthesized two-dimensional mammography: A systematic review and meta-analysis

 

by Baoqi Zeng, Kai Yu, Le Gao, Xueyang Zeng, Qingxin Zhou 

 

The Breast: Published, July 21, 2021

 

Purpose

We conducted a systematic review and meta-analysis to compare the screening performance of synthesized mammography (SM) plus digital breast tomosynthesis (DBT) with digital mammography (DM) plus DBT or DM alone.

Methods

Medline, Embase, Web of Science, and the Cochrane Library databases were searched from January 2010 to January 2021. Eligible population-based studies on breast cancer screening comparing SM/DBT with DM/DBT or DM in asymptomatic women were included. A random-effect model was used in this meta-analysis. Data were summarized as risk differences (RDs), with 95 % confidence intervals (CIs).

Results

Thirteen studies involving 1,370,670 participants were included. Compared with DM/DBT, screening using SM/DBT had similar breast cancer detection rate (CDR) (RD = −0.1/1000 screens, 95 % CI = −0.4 to 0.2, p = 0.557, I2 = 0 %), but lower recall rate (RD = −0.56 %, 95 % CI = −1.03 to −0.08, p = 0.022, I2 = 90 %) and lower biopsy rate (RD = −0.33 %, 95 % CI = −0.56 to −0.10, p = 0.005, I2 = 78 %). Compared with DM, SM/DBT improved CDR (RD = 2.0/1000 screens, 95 % CI = 1.4 to 2.6, p < 0.001, I2 = 63 %) and reduced recall rate (RD = −0.95 %, 95 % CI = −1.91 to −0.002, p = 0.049, I2 = 99 %). However, SM/DBT and DM had similar interval cancer rate (ICR) (RD = 0.1/1000 screens, 95 % CI = −0.6 to 0.8, p = 0.836, I2 = 71 %) and biopsy rate (RD = −0.05 %, 95 % CI = −0.35 to 0.24, p = 0.727, I2 = 93 %).

Conclusions

Screening using SM/DBT has similar breast cancer detection but reduces recall and biopsy when compared with DM/DBT. SM/DBT improves CDR when compared with DM, but they have little difference in ICR. SM/DBT could replace DM/DBT in breast cancer screening to reduce radiation dose.

A pilot study evaluating the effect of early physical therapy on pain and disabilities after breast cancer surgery: Prospective randomized control trail

 

A pilot study evaluating the effect of early physical therapy on pain and disabilities after breast cancer surgery: Prospective randomized control trail

 

by Ifat Klein, Leonid Kalichman, Noy Chen, Sergio Susmallian 

 

The Breast: Published, July 21, 2021

 

Background

Morbidity of the shoulders after breast cancer (BC) surgery is a common side effect that includes; persistent pain, function limitation, and decreased range of motion (ROM). This study examines the effect of early physical therapy (PT) and patient's education on these morbidities.

Methods

A prospective, randomized clinical trial was conducted at a single medical center from October 2018 until April 2019. Women scheduled for breast cancer surgery were divided into intervention or control as standard care. The intervention included a PT treatment that included exercise instructions from the first postoperative day. Pain levels, upper limb function, ROM, and complications were measured.

Results

The study includes 157 women (mean age, 52.2 ± 12.9). Early PT reduced pain levels at the first month (NPRS 1.5 ± 1.2) and six months (NPRS 0.5 ± 0.8), compared with control (NPRS 2.1 ± 1.4, 1.0 ± 1.2), p = 0.019 and p = 0.011, respectively. Subdivision of the sample into small and extensive surgeries revealed additional positive effect for the intervention six months postoperatively on functional disabilities, p = 0.004 and p = 0.032 respectively. No complications attributable to the intervention were recorded.

Conclusions

Early PT and patient education reduces pain levels, and may improve function disabilities, without causing postoperative complications, although a larger study is needed to achieve unequivocal results.

 

Quality of life of therapies for hormone receptor positive advanced/metastatic breast cancer: Regulatory aspects and clinical impact in Europe

 

Quality of life of therapies for hormone receptor positive advanced/metastatic breast cancer: Regulatory aspects and clinical impact in Europe

 

by L. Moscetti, I. Sperdutia, A. Frassoldati, A. Musolino, C. Nasso, A. Toss, C. Omarini, M. Dominici, F. Piacentini 

The Breast: Published, July 14, 2021

Purpose

Overall survival in breast cancer patients receiving a delayed deep inferior epigastric perforator (DIEP) flap breast reconstruction is better than in those without delayed breast reconstruction. This study aimed at determining the impact of socioeconomic status (SES) and comorbidity on these observations.

Materials and methods

This matched cohort study included all consecutive women undergoing a delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013. Controls had not received any delayed breast reconstruction and were relapse-free after a corresponding follow-up interval. Matching was by year of and age at mastectomy, tumour stage and lymph node status. Charlson Comorbidity Index (CCI) and socioeconomic data were obtained from national registers. Associations with breast cancer-specific (BCSS) and overall survival (OS) were investigated by Kaplan-Meier survival estimates and Cox proportional hazard regression analysis.

Results

Women in the DIEP group (N = 254) more often continued education after primary school (88.6% versus 82.6%, P = 0.026), belonged to the high-income group (76.0% versus 63.1%, P < 0.001), were in a partnership (57.1% versus 55.7%, P = 0.024) and healthier (median CCI 1.00 (range 0–13) versus 2.00 (range 0–16), P = 0.021) than the control group (N = 729). After adjustment for tumour and treatment factors, SES and comorbidity, OS remained significantly better for the DIEP group than the control group (HR 2.27, 95% CI 1.44–3.55).

Conclusion

Women with a delayed DIEP flap reconstruction are a subgroup of higher socioeconomic status and better health. Higher survival estimates for the DIEP group persisted after adjusting for those differences, suggesting the presence of further unmeasured covariates.

The 10-Year Experience with Volume Distribution Mastopexy: A Novel, Safe, and Efficient Method for Breast Rejuvenation

 

Tumor-to-Nipple Distance and the Safety of Nipple-Sparing Mastectomy

 

by Wu, Zhen-Yu; Han, Hyun Ho; Eom, Jin Sup; Ahn, Sei Hyun; Ko, BeomSeok 

 

Plastic and Reconstructive Surgery: July 2021 - Volume 148 - Issue 1 - p 158e-159e

 

Nipple-sparing mastectomy is an oncoplastic surgical technique that can substantially optimize the aesthetic outcomes of breast reconstruction by preserving the nipple-areola complex, and it is being increasingly used in the treatment of breast cancer. The indications for nipple-sparing mastectomy remain controversial, however, especially with respect to the tumor-to-nipple distance…

Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients

 

Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients

 

by I-Chun Chen, Fu-Chang Hu, Ching-Hung Lin, Shu-Min Huang, Dwan-Ying Chang, Ann-Lii Cheng, Yen-Shen Lu 

 

The Breast:  VOLUME 59, P211-220, OCTOBER 01, 2021

 

Background

This meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody.

Methods

The NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999–November 2017. Treatment arms with shorter PFS were considered as the “control” arm, whereas those with longer PFS as the “test” arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses.

Results

Twenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68–0.78) and median OS (HR = 0.82, 95% CI: 0.77–0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p < 0.001) and linearly correlated, which was not found with any non-anti-HER2 antibody drug differences.

Conclusions

Anti-HER2 antibody in patients with HER2-positive mBC prolonged OS more than PFS and mandates further investigation.

Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, HER2-negative early breast cancer: A meta-analysis of randomized clinical trials

 

Adjuvant CDK4/6 inhibitors combined with endocrine therapy in HR-positive, HER2-negative early breast cancer: A meta-analysis of randomized clinical trials

 

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

 

The Breast: VOLUME 59, P165-175, OCTOBER 01, 2021

 

Background

The benefit of adjuvant cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with endocrine therapy (ET) in hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) early breast cancer (EBC) is uncertain. Hence, we performed a meta-analysis to determine the efficacy and safety of adjuvant CDK4/6 inhibitors plus ET and to identify potential preferred subpopulations for this regimen.

Methods

A literature search was conducted in PubMed, Embase, Cochrane databases up to Jan 15, 2021. Hazard ratios (HRs) for invasive disease-free survival (IDFS) and risk ratios (RRs) for grade 3/4 adverse events (AEs) and treatment discontinuation were extracted. Analysis with predefined subgroup variables was done. Trial sequential analysis (TSA) was performed to assess the conclusiveness of survival outcomes.

Results

Three trials were eligible (N = 12647). Compared with ET, adjuvant CDK4/6 inhibitors with ET prolonged IDFS in patients with HR+/HER2- EBC (HR 0.87, 95% CI 0.76–0.98, p = 0.03, I2 = 19%), with positive therapeutic responses observed in patients with N2/N3 nodal status (HR 0.83, 95% CI 0.71–0.97, p = 0.02, I2 = 0%). None of the cumulative z-curves crossed the trial monitoring boundaries in TSA, and no reliable conclusion could be drawn. The combination treatment carried a higher risk of grade 3/4 AEs (RR 4.14, 95% CI 3.33–5.15, p < 0.00001) and an increase in treatment discontinuation due to AEs (RR 19.16, 95% CI 9.27–39.61, p < 0.00001).

Conclusions

Adjuvant CDK4/6 inhibitors with ET might provide survival benefit in HR+/HER2- EBC. A statistically significantly improved IDFS was only observed in N2/N3 subgroup. However, overall evidence favoring the use of this combination regimen was inadequate.

Quality indicators for breast cancer care: A systematic review

 Quality indicators for breast cancer care: A systematic review

 by Marta Maes-Carballo, Yolanda Gómez-Fandiño, Ayla Reinoso Hermida, Carlos Roberto Estrada-López, Manuel Martín-Díaz, Khalid Saeed Khan, Aurora Bueno-Cavanillas 

 

The Breast: VOLUME 59, P221-231, OCTOBER 01, 2021

 

Objectives

We evaluated breast cancer (BC) care quality indicators (QIs) in clinical pathways and integrated health care processes.

Methods

Following protocol registration (Prospero no: CRD42021228867), relevant documents were identified, without language restrictions, through a systematic search of bibliographic databases (EMBASE, Scopus, Web of Science, MEDLINE), health care valuable representatives and the World Wide Web in April 2021. Data concerning QIs, measurement tools and compliance standards were extracted from European and North American sources in duplicate with 98% reviewer agreement.

Results

There were 89 QIs found from 22 selected documents (QI per document mean 13.5 with standard deviation 11.9). The Belgian (38 QIs) and the EUSOMA (European Society of Breast Cancer Specialists) (34 QIs) documents were the ones that best reported the QIs. No identical QI was identified in all the documents analysed. There were 67/89 QIs covering processes (75.3%) and 11/89 (12.4%) for each structure and outcomes QIs. There were 21/89 QIs for diagnosis (30.3%), 43/89 for treatment (48.3%), and 19/89 for staging, counselling, follow-up and rehabilitation (21.4%). Of 67 process QIs and 11 outcome QIs, 20/78 (26%) did not report a minimum standard of care. Shared decision making was only included as a QI in the Italian document.

Conclusion

More than half of countries have not established a national clinical pathway or integrated breast cancer care process to achieve the excellence of BC care. There was heterogeneity in QIs for the evaluation of BC care quality. Over two-thirds of the clinical pathways and integrated health care processes did not provide a minimum auditable standard of care for compliance, leaving open the definition of best practice. There is a need for harmonisation of BC care QIs.

Diagnosis, biology and epidemiology of oligometastatic breast cancer

 

Diagnosis, biology and epidemiology of oligometastatic breast cancer

 

by Jean-Louis Lacaze, Richard Aziza, Ciprian Chira, Eleonora De Maio, Françoise Izar, Eva Jouve, Carole Massabeau, Anne Pradines, Gabrielle Selmes, Mony Ung, Slimane Zerdoud, Florence Dalenc 

The Breast: VOLUME 59, P144-156, OCTOBER 01, 2021

Highlights

• The incidence of oligometastatic breast cancer is unknown.

• Only one publication provides information regarding the biology of these cancers.

• Oligometastatic breast cancer and metastatic site definitions should be harmonized.

• Prospective observational cohort studies are needed.

Abstract

Does oligometastatic breast cancer (OMBC) deserve a dedicated treatment? Although some authors recommend multidisciplinary management of OMBC with a curative intent, there is no evidence proving this strategy beneficial in the absence of a randomized trial. The existing literature sheds little light on OMBC. Incidence is unknown; data available are either obsolete or biased; there is no consensus on the definition of OMBC and metastatic sites, nor on necessary imaging techniques. However, certain proposals merit consideration. Knowledge of eventual specific OMBC biological characteristics is limited to circulating tumor cell (CTC) counts. Given the data available for other cancers, studies on microRNAs (miRNAs), circulating tumor DNA (ctDNA) and genomic alterations should be developed Finally, safe and effective therapies do exist, but results of randomized trials will not be available for many years. Prospective observational cohort studies need to be implemented.

Triple-negative breast cancer outcomes: Does AJCC 8th staging improve chemotherapy decision-making

 

Triple-negative breast cancer outcomes: Does AJCC 8th staging improve chemotherapy decision-making

by Chen-Lu Lian, Guan-Qiao Li, Ping Zhou, Jun Wang, Zhen-Yu He, San-Gang Wu 

The Breast: VOLUME 59, P117-123, OCTOBER 01, 2021

Purpose

To investigate the effect of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging on chemotherapy decision-making for triple-negative breast cancer (TNBC) patients with T1-2N0M0 disease.

Methods

Patients diagnosed with T1-2N0M0 TNBC were retrieved from the Surveillance, Epidemiology, and End Results program. Statistical methods including Kaplan-Meier survival curve, receiver operating characteristics curve, and Cox proportional hazard model.

Results

We identified 12,156 patients, including 9371 (77.1%) patients who received chemotherapy. Overall, 57.4% of patients (n = 6975) were upstaged after being reassigned by the 8th AJCC staging. However, the 8th staging of AJCC did not have a greater prognostic value compared to the 7th staging (P = 0.064). The receipt of chemotherapy significantly improved the breast cancer-specific survival for stage T1c and T2 tumors (P < 0.001), but not for stage T1a (P = 0.188) and T1b (P = 0.376) tumors. Using AJCC 8th staging, chemotherapy benefit was only found in stage IIA patients (P = 0.002), but not for stage IA (P = 0.653) and IB (P = 0.492) patients. There were 9564 patients with stage T1c and T2 diseases and 4979 patients with 8th AJCC stage IIA disease. Therefore, approximately half of patients (47.9%, n = 4585) may be safe to omit chemotherapy using the AJCC 8th staging compared to the current chemotherapy recommendation for T1-2N0M0 TNBC.

Conclusion

The 8th AJCC staging system did not demonstrate the superior discriminatory ability of prognostic stratification than the 7th AJCC staging system in T1-2N0M0 TNBC. However, this new AJCC staging could more accurately predict the chemotherapy benefit, thereby enabling more patients to avoid unnecessary chemotherapy.

Characteristics and outcomes of COVID-19 infection in 45 patients with breast cancer: A multi-center retrospective study in Hubei, China

 

Characteristics and outcomes of COVID-19 infection in 45 patients with breast cancer: A multi-center retrospective study in Hubei, China

 

by Jielin Wei, Mengjiao Wu, Jing Liu, Xu Wang, Hua Yang, Pengfei Xia, Ling Peng, Yu Huang, Cuiwei Liu, Zihan Xia, Chuang Chen, Yanxia Zhao 

The Breast: VOLUME 59, P102-109, OCTOBER 01, 2021

 

Background

The COVID-19 pandemic is a significant worldwide health crisis. Breast cancer patients with COVID-19 are fragile and require particular clinical care. This study aimed to identify the clinical characteristics of breast cancer patients with COVID-19 and the risks associated with anti-cancer treatment.

Methods

The medical records of breast cancer patients with laboratory-confirmed COVID-19 were collected among 9559 COVID-19 patients from seven designated hospitals from 13th January to 18th March 2020 in Hubei, China. Univariate and multivariate analyses were performed to assess risk factors for COVID-19 severity.

Results

Of the 45 breast cancer patients with COVID-19, 33 (73.3%) developed non-severe COVID-19, while 12 (26.7%) developed severe COVID-19, of which 3 (6.7%) patients died. The median age was 62 years, and 3 (6.7%) patients had stage IV breast cancer. Univariate analysis showed that age over 75 and the Eastern Cooperative Oncology Group (ECOG) score were associated with COVID-19 disease severity (P < 0.05). Multivariate analysis showed that patients who received chemotherapy within 7 days had a significantly higher risk for severe COVID-19 (logistic regression model: RR = 13.886, 95% CI 1.014–190.243, P = 0.049; Cox proportional hazards model: HR = 13.909, 95% CI 1.086–178.150, P = 0.043), with more pronounced neutropenia and higher LDH, CRP and procalcitonin levels than other patients (P < 0.05).

Conclusions

In our breast cancer cohort, the severity of COVID-19 could be associated with baseline factors such as age over 75 and ECOG scores. Chemotherapy within 7 days before symptom onset could be a risk factor for severe COVID-19, reflected by neutropenia and elevated LDH, CRP and procalcitonin levels.

Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations

 

Biological and clinical features of triple negative Invasive Lobular Carcinomas of the breast. Clinical outcome and actionable molecular alterations

by Fabio Conforti, Laura Pala, Eleonora Pagan, Elena Guerini Rocco, Vincenzo Bagnardi, Emilia Montagna, Giulia Peruzzotti, Tommaso De Pas, Caterina Fumagalli, Silvana Pileggi, Chiara Pesenti, Sergio Marchini, Giovanni Corso, Caterina Marchio’, Anna Sapino, Rossella Graffeo, Laetitia Collet, Philippe Aftimos, Christos Sotiriou, Martine Piccart, Richard D. Gelber, Giuseppe Viale, Marco Colleoni, Aron Goldhirsch 

The Breast:  VOLUME 59, P94-101, OCTOBER 01, 2021

Background

We report here for the first time, a comprehensive characterization of biological and clinical features of early-stage triple negative Invasive Lobular Carcinomas(TN-ILCs)

Methods

We analyzed all consecutive patients with early-stage TN-ILC operated at two reference cancer-centers between 1994 and 2012.

Primary objective was to assess the invasive disease-free survival(iDFS).

Co-primary objective was to assess biological features of TN-ILCs, including molecular intrinsic subtypes based on PAM-50 assay, expression of androgen receptor (AR) and mutational status of ERBB2-gene.

Additionally, DNA mutational status of an independent cohort of 45 TN-ILCs from three databases were analyzed, to confirm mutations in ERBB2-gene and to identify other recurrently mutated genes.

Results

Among 4152 ILCs, 74(1.8%) were TN and were analyzed.

The iDFS at 5 and 10 years of FUP were 50.4%(95%CI,38.0–61.6) and 37.2%(95%CI,25.5–48.8), respectively.

The molecular subtype was defined through PAM50-classifier for 31 out of 74 TN-ILCs: 48% were Luminal-A(15/31), 3% luminal-B(1/31), 32% HER2-enriched (10/31), and only 16% basal-like(5/31).

Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 94% of luminal tumors versus 53% in non-luminal tumors; p-value = 0.001).

20% of TN-ILCs analyzed(7/35), harbored a pathogenetic and actionable mutation in the ERBB2-gene. Analysis of the independent cohort of 45 TN-ILCs from three different databases, confirmed similar percentage of pathogenetic and actionable mutations in ERBB2-gene(20%; 9/45).

Among the top 10 molecular pathways significantly enriched for recurrently mutated genes in TN-ILCs(FDR<0.05), there were ErbB-signaling and DNA-damage-response pathways.

Conclusions

TN-ILCs are rare tumors with poor prognosis. Their specific biological features require newly defined targeted therapeutic strategies