Thursday, 7 October 2021

Breast Surgery Bulletin: October 2021


The Goldilocks Procedure with and without Implant-Based Immediate Breast Reconstruction in Obese Patients: The Mayo Clinic Experience


by Bustos, Samyd S.; Nguyen, Minh-Doan; Harless, Christin A.; Tran, Nho V.; Martinez-Jorge, Jorys; Lin, Jason; Forte, Antonio J.; Casey, William J. III; Boughey, Judy C.; McLaughlin, Sarah A.; Gray, Richard; Manrique, Oscar J.


Plastic and Reconstructive Surgery: October 2021 - Volume 148 - Issue 4 - p 703-716



Obesity is a risk factor for complications in breast reconstruction. Thus, implant-based immediate breast reconstruction in obese women may be controversial. The authors analyzed obese patients who underwent skin-sparing mastectomy using Wise-pattern incisions (Goldilocks procedure) and compared outcomes between two groups: Goldilocks with immediate breast reconstruction and Goldilocks only.


A retrospective review was performed of patients with a body mass index of 30 kg/m2 or higher who underwent the Goldilocks procedure at the Mayo Clinic Health System from 2012 to 2019. Data were extracted from electronic medical records. Minor complications (partial-thickness wound dehiscence or flap necrosis, or tissue expander/implant malposition) and major complications (full-thickness wound dehiscence or flap necrosis, capsular contracture, tissue expander/implant explantation, or unplanned reoperation or readmission) were compared between groups. Patient-reported outcomes using BREAST-Q questionnaires were also assessed.


One hundred five patients (181 breasts) were included. Mean ± SEM age and body mass index were 57.1 ± 10.4 years and 37.9 ± 5.8 kg/m2 for the Goldilocks-only group and 51.5 ± 1.1 years and 35.5 ± 0.4 kg/m2 for the Goldilocks with immediate breast reconstruction group, respectively. Median follow-up time was 15.1 months (interquartile range, 10.0 to 28.6 months). Overall, 96 breasts underwent the Goldilocks-only procedure and 85 Goldilocks with immediate breast reconstruction. Multivariable analyses revealed a higher rate of minor complications (adjusted hazard ratio, 2.83; 95 percent CI, 1.22 to 7.02) and major complications (adjusted hazard ratio, 2.26; 95 percent CI, 1.25 to 4.24) in the Goldilocks with immediate breast reconstruction group compared with the Goldilocks-only group, at any given time. Patient satisfaction was not statistically different between groups.


The Goldilocks procedure is a feasible breast reconstructive option in obese patients; however, when it is performed with immediate breast reconstruction, it is associated with higher rates of complications. For patients with a body mass index of 40 kg/m2 or greater, the authors recommend the Goldilocks-only procedure or delayed reconstruction.


Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients


by Fabio Corsi, Sara Albasini, Luca Sorrentino, Giulia Armatura, Claudia Carolla, Corrado Chiappa, Francesca Combi, Annalisa Curcio, Angelica Della Valle, Guglielmo Ferrari, Maria Luisa Gasparri, Oreste Gentilini, Matteo Ghilli, Chiara Listorti, Stefano Mancini, Peter Marinello, Francesco Meani, Simone Mele, Anna Pertusati, Manuela Roncella, Francesca Rovera, Adele Sgarella, Giovanni Tazzioli, Daniela Tognali, Secondo Folli 


The Breast:  VOLUME 60, P131-137, DECEMBER 01, 2021



Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized.

Patients and methods

1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR).


Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75–0.80). After external validation the accuracy of the nomogram was confirmed.


The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.


Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study


by Sudeep Gupta, Ghanashyam Biswas, Suresh Babu, Tanveer M. Maksud, Kuntegowdennahalli C. Lakshmaiah, Jayanti G. Patel, Gopal Raja, Rakesh R. Boya, Pramod Patil, Kakali Choudhury, Shailesh A. Bondarde, Rakesh S. Neve, Guruprasad Bhat, Gopichand Mamillapalli, Apurva A. Patel, Piyush Patel, Nisarg Joshi, Vinay Bajaj, Mujtaba A. Khan 


The Breast: VOLUME 60, P147-154, DECEMBER 01, 2021



To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy.


In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II.


Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45–41.81%) and 22.41% (13/58, 95%CI: 11.68–33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08–96.00%) and 82.76% (48/58; 95%CI: 73.04–92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41–79.50%) and 50.00% (29/58; 95%CI: 40.40–67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events.


FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.



Treatment and outcomes of older versus younger women with HER2-positive metastatic breast cancer in the real-world national ESME database


tby Annonay Mylène, Gauquelin Lisa, Geiss Romain, Ung Mony, Cristol-Dalstein Laurence, Mouret-Reynier Marie-Ange, Goncalves Anthony, Abadie-Lacourtoisie Sophie, Francois Eric, Perrin Christophe, Le Fel Johan, Lorgis Véronique, Servent Véronique, Uwer Lionel, Jouannaud Christelle, Leheurteur Marianne, Joly Florence, Campion Loic, Courtinard Coralie, Villacroux Olivier, Petit Thierry, Soubeyran Pierre, Terret Catherine, Bellera Carine, Brain Etienne, Delaloge Suzette 


The Breast: VOLUME 60, P138-146, DECEMBER 01, 2021



Treatment and outcomes of patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have dramatically improved over the past 20 years. This work evaluated treatment patterns and outcomes according to age.


Women who initiated a treatment for HER2+ MBC between 2008 and 2016 in one of the 18 French comprehensive centers part of the ESME program were included. Objectives were the description of first-line treatment patterns, overall survival (OS), first-line progression-free survival (PFS), and prognostic factors among patients aged 70 years or more (70+), or less than 70 (<70).


Of 4045 women diagnosed with an HER2+ MBC, 814 (20%) were 70+. Standard first-line treatment (chemotherapy combined with an anti-HER2 therapy) was prescribed in 65% of 70+ versus 89% of <70 patients (p < 0.01). Median OS was 49.2 (95% CI, 47.1–52.4), 35.3 (95% CI, 31.5–37.0) and 54.2 months (95% CI, 50.8–55.7) in the whole population, in patients 70+ and <70, respectively. Corresponding median PFS1 were 12.8 (95% CI, 12.3–13.3), 11.1 (95% CI, 10.0–12.3) and 13.2 months (95% CI, 12.7–13.9), respectively. In 70+ women, initiation of non-standard first-line treatment had an independent detrimental time-varying effect on both OS and PFS (HR on OS at 1 year: chemotherapy without anti-HER2 2.79 [95% CI: 2.05–3.79]; endocrine therapy and/or anti-HER2 1.96 [95% CI: 1.43–2.69]).


In this large retrospective real-life database, older women with HER2+ MBC received standard first-line treatment less frequently than younger ones. This was independently associated with a worse outcome, but confounding factors and usual selection biases cannot be ruled out.


Factors involved in treatment decision making for women diagnosed with ductal carcinoma in situ: A qualitative study


by Amy Hatton, Natalie Heriot, John Zalcberg, Darshini Ayton, Jill Evans, David Roder, Boon H. Chua, Jolyn Hersch, Jocelyn Lippey, Jane Fox, Christobel Saunders, G.Bruce Mann, Jane Synnot, Robin J. Bell 


The Breast: VOLUME 60, P123-130, DECEMBER 01, 2021



•Factors other than the characteristics of the DCIS were involved in decisions about management.

•There was a lack of understanding about diagnosis and prognosis.

•There was inconsistent involvement by women in decision making about management.

•Factors such as perception of mastectomy and radiotherapy could act as barriers or facilitators in decision making.


Whilst some of the diversity in management of women with ductal carcinoma in situ (DCIS) may be explained by tumour characteristics, the role of patient preference and the factors underlying those preferences have been less frequently examined. We have used a descriptive qualitative study to explore treatment decisions for a group of Australian women diagnosed with DCIS through mammographic screening. Semi-structured telephone interviews were performed with 16 women diagnosed with DCIS between January 2012 and December 2018, recruited through the LifePool dataset (a subset of BreastScreen participants who have agreed to participate in research). Content analysis using deductive coding identified three themes: participants did not have a clear understanding of their diagnosis or prognosis; reported involvement in decision making about management varied; specific factors including the psychosexual impact of mastectomy and perceptions of radiotherapy, could act as barriers or facilitators to specific decisions about treatment.

The treatment the women received was not simply determined by the characteristics of their disease. Interaction with the managing clinician was pivotal, however many other factors played a part in individual decisions. Recognising that decisions are not purely a function of disease characteristics is important for both women with DCIS and the clinicians who care for them.


Machine learning to predict individual patient-reported outcomes at 2-year follow-up for women undergoing cancer-related mastectomy and breast reconstruction (INSPiRED-001)


by André Pfob, Babak J. Mehrara, Jonas A. Nelson, Edwin G. Wilkins, Andrea L. Pusic, Chris Sidey-Gibbons 


The Breast: VOLUME 60, P111-122, DECEMBER 01, 2021



Women undergoing cancer-related mastectomy and reconstruction are facing multiple treatment choices where post-surgical satisfaction with breasts is a key outcome. We developed and validated machine learning algorithms to predict patient-reported satisfaction with breasts at 2-year follow-up to better inform the decision-making process for women with breast cancer.


We trained, tested, and validated three machine learning algorithms (logistic regression (LR) with elastic net penalty, Extreme Gradient Boosting (XGBoost) tree, and neural network) to predict clinically important differences in satisfaction with breasts at 2-year follow-up using the validated BREAST-Q. We used data from 1553 women undergoing cancer-related mastectomy and reconstruction who were followed-up for two years at eleven study sites in North America from 2011 to 2016. 10-fold cross-validation was used to train and test the algorithms on data from 10 of the 11 sites which were further validated using the additional site's data. Area-under-the-receiver-operating-characteristics-curve (AUC) was the primary outcome measure.


Of 1553 women, 702 (45.2%) experienced an improved satisfaction with breasts and 422 (27.2%) a decreased satisfaction. In the validation set (n = 221), the algorithms showed equally high performance to predict improved or decreased satisfaction with breasts (all P > 0.05): For improved satisfaction AUCs were 0.86–0.87 and for decreased satisfaction AUCs were 0.84–0.85.


Long-term, individual patient-reported outcomes for women undergoing mastectomy and breast reconstruction can be accurately predicted using machine learning algorithms. Our algorithms may be used to better inform clinical treatment decisions for these patients by providing accurate estimates of expected quality of life.


Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial


The Lancet Oncology: VOLUME 22, ISSUE 10, P1458-1467, OCTOBER 01, 2021



The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2–3 years of letrozole in postmenopausal patients with breast cancer who have already received 2–3 years of tamoxifen.


This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy. Women were eligible if they were postmenopausal at the time of study entry, had stage I–III histologically proven and operable invasive hormone receptor-positive breast cancer, had received adjuvant tamoxifen therapy for at least 2 years but no longer than 3 years and 3 months, had no signs of disease recurrence, and had an Eastern Cooperative Oncology Group performance status of 2 or lower. Patients were randomly assigned (1:1) to receive 2–3 years (control group) or 5 years (extended group) of letrozole (2·5 mg orally once a day). Randomisation, with stratification by centre, with permuted blocks of size 12, was done with a centralised, interactive, internet-based system that randomly generated the treatment allocation. Participants and investigators were not masked to treatment assignment. The primary endpoint was invasive disease-free survival in the intention-to-treat population. Safety analysis was done for patients who received at least 1 month of study treatment. This trial was registered with EudraCT, 2005-001212-44, and ClinicalTrials.govNCT01064635.


Between Aug 1, 2005, and Oct 24, 2010, 2056 patients were enrolled and randomly assigned to receive letrozole for 2–3 years (n=1030; control group) or for 5 years (n=1026; extended group). After a median follow-up of 11·7 years (IQR 9·5–13·1), disease-free survival events occurred in 262 (25·4%) of 1030 patients in the control group and 212 (20·7%) of 1026 in the extended group. 12-year disease-free survival was 62% (95% CI 57–66) in the control group and 67% (62–71) in the extended group (hazard ratio 0·78, 95% CI 0·65–0·93; p=0·0064). The most common grade 3 and 4 adverse events were arthralgia (22 [2·2%] of 983 patients in the control group vs 29 [3·0%] of 977 in the extended group) and myalgia (seven [0·7%] vs nine [0·9%]). There were three (0·3%) serious treatment-related adverse events in the control group and eight (0·8%) in the extended group. No deaths related to toxic effects were observed.


In postmenopausal patients with breast cancer who received 2–3 years of tamoxifen, extended treatment with 5 years of letrozole resulted in a significant improvement in disease-free survival compared with the standard 2–3 years of letrozole. Sequential endocrine therapy with tamoxifen for 2–3 years followed by letrozole for 5 years should be considered as one of the optimal standard endocrine treatments for postmenopausal patients with hormone receptor-positive breast cancer.



A Comparison of Surgical Complications in Patients Undergoing Delayed versus Staged Tissue-Expander and Free-Flap Breast Reconstruction


by Shammas, Ronnie L.; Cason, Roger W.; Sergesketter, Amanda R.; Glener, Adam D.; Broadwater, Gloria; Hollins, Andrew; Le, Elliot; Marks, Caitlin; Atia, Andrew N.; Orr, Jonah P.; Hollenbeck, Scott T. 


Plastic and Reconstructive Surgery: September 2021 - Volume 148 - Issue 3 - p 501-509


Background: Patients undergoing mastectomy may not be candidates for immediate free-flap breast reconstruction because of medical comorbidities or postmastectomy radiation therapy. In this setting, flap reconstruction may be intentionally delayed or staged with tissue expander placement (“delayed-immediate” reconstruction). The optimal reconstructive choice and incidence of complications for these approaches remain unclear.

Methods: The authors retrospectively identified patients who underwent delayed [n = 140 (72 percent)] or staged [n = 54 (28 percent)] abdominal free-flap breast reconstruction between 2010 and 2018 and compared the incidence of postoperative complications.

Results: Patients undergoing staged reconstruction had a higher overall incidence of perioperative complications, including surgical-site infection (40.7 percent versus 6.5 percent; p < 0.001), wound healing complications (29.6 percent versus 12.3 percent; p = 0.004), hematoma (11.1 percent versus 0.7 percent; p < 0.001), and return to the operating room (27.8 percent versus 4.4 percent; p < 0.0001). These complications occurred predominately during the expansion stage, resulting in an 18.5 percent (n = 10) rate of tissue expander failure. Mean time from mastectomy to flap reconstruction was 476.8 days (delayed, 536.4 days; staged, 322.4 days; p < 0.001). At the time of flap reconstruction, there was no significant difference in the incidence of complications between the staged cohort versus the delayed cohort, including microsurgical complications (1.9 percent versus 4.3 percent; p = 0.415), total flap loss (0 percent versus 2.1 percent; p = 0.278), or fat necrosis (5.6 percent versus 5.0 percent; p = 0.875).

Conclusions: The aesthetic and psychosocial benefits of staged free-flap breast reconstruction should be balanced with the increased risk of perioperative complications as compared to a delayed approach. Complications related to definitive flap reconstruction do not appear to be affected by the approach taken at the time of mastectomy. 

Clinical Question/Level of Evidence: Therapeutic, III.


Comparing Outcomes of Wise-Pattern, Two-Stage Breast Reduction-Reconstruction with and without Acellular Dermal Matrix


by Patel, Ashraf A.; Kayaleh, Hana; Sala, Luke A.; Peterson, Dylan J.; Upadhyaya, Prashant K

Plastic and Reconstructive Surgery: September 2021 - Volume 148 - Issue 3 - p 511-521

Background: Aesthetic results in breast reconstruction for ptotic/obese breasts may be improved when using Wise-pattern closures compared with nipple-sparing mastectomies. In two-stage reconstruction, acellular dermal matrix is commonly used to support the prosthesis. This study tests the efficacy of an alternate technique that uses deepithelialized excess breast skin in lieu of acellular dermal matrix. To better understand whether acellular dermal matrix is necessary, the authors compared postoperative outcomes from reduction-reconstructions that used matrix to those that did not.

Methods: The authors retrospectively reviewed the outcomes of patients who underwent staged breast reconstruction following Wise-pattern closures between September of 2016 and October of 2019. Two cohorts were created based on whether acellular dermal matrix was used. Charts were reviewed for incidence of postoperative complications.

Results: A total of 164 breasts were reconstructed in 85 female patients. The acellular dermal matrix cohort consisted of 68 breasts, whereas the non–acellular dermal matrix cohort included 96 breasts. After the first stage, the incidence of one or more complications was similar between cohorts (acellular dermal matrix, 32.4 percent; nonmatrix, 35.4 percent; p = 0.684). Minor infection rates were significantly higher in reconstructions using acellular dermal matrix (16.2 percent versus 6.3 percent; p = 0.040). After the second stage, the complication incidence was also similar between cohorts (acellular dermal matrix, 16.2 percent; nonmatrix, 13.5 percent; p = 0.638). Final follow-up time was 445.2 days.

Conclusions: Overall complication rates following both stages of reconstruction were similar with and without acellular dermal matrix. When acellular dermal matrix was used, minor infection rates were higher following expander placement. In patients desiring a reduction-reconstruction, the authors find the deepithelialized dermal flap provides ample prosthesis support, without the need for acellular dermal matrix. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Thursday, 2 September 2021

Breast Surgery Bulletin: September 2021


Axillary surgery in node-positive breast cancer

 by Nadia Maggi, Rahel Nussbaumer, Liezl Holzer, Walter P. Weber 

 The Breast: August 31, 2021


• Current indications for performing axillary lymph node dissection.

• De-escalating axillary surgery strategies in node-positive breast cancer.

• New concept for clinically node-positive breast cancer.


Long-term follow-up data from multicenter phase III non-inferiority trials confirmed the safety of omission of axillary dissection in selected patients with clinically node-negative, sentinel node-positive breast cancer. Several ongoing trials investigate extended eligibility of the Z0011 protocol in the adjuvant setting. De-escalation of axillary surgery in patients with clinically node-positive breast cancer is currently limited to the neoadjuvant setting, where the sentinel procedure is used to determine nodal pathological complete response. Targeted axillary dissection lowers the false-negative rate of the sentinel procedure, which, however, is consistently associated with a very low risk of axillary recurrence in several recent single-center series. Axillary dissection remains standard care in patients with residual disease after neoadjuvant chemotherapy while the results of Alliance A011202 are pending. The TAXIS trial investigates the role of tailored axillary surgery in patients with clinically node-positive breast cancer, a novel concept designed to selectively remove positive nodes in the adjuvant and neoadjuvant setting.


Implant-Based Breast Reconstruction Outcomes Using Oxychlorosene for Pocket Irrigation

  by Dawson, Steven E.; Bamba, Ravinder; Tran, Phu C.; Mailey, Brian; Lin, Jenny; Lester, Mary; Sinha, Mithun; Hassanein, Aladdin H. 

 Plastic and Reconstructive Surgery: September 2021 - Volume 148 - Issue 3 - p 518e-520e

 Breast implants are placed in over 400,000 patients annually, but up to 29 percent have postoperative infections.1 Pocket irrigation with antiseptic solutions is used to reduce implant contamination. The optimal irrigation solution and the efficacy of individual practices are unclear. Oxychlorosene sodium has been used historically as an antiseptic, but there are no data on its effectiveness in breast implant surgery. It is a derivative of hypochlorous acid and is a powerful antimicrobial.2 A survey of American Society of Plastic Surgeons members showed that 14 percent of responders used oxychlorosene for breast implant irrigation.3 Our institution has commonly used oxychlorosene irrigation. Following approval from our institutional review board, patients who underwent implant-based reconstruction after mastectomy with use of oxychlorosene breast pocket irrigation between 2016 to 2018 were retrospectively reviewed…


Uptake of bilateral-risk-reducing-mastectomy: Prospective analysis of 7195 women at high-risk of breast cancer

by D.Gareth Evans, Ashu Gandhi, Julie Wisely, Tara Clancy, Emma R. Woodward, James Harvey, Lyndsey Highton, John Murphy, Lester Barr, Sacha J. Howell, Fiona Lalloo, Elaine F. Harkness, Anthony Howell 

The Breast: August 26, 2021


•BRRM continues even 20 years post original breast cancer risk assessment.

•Potential triggers include death of mother/sister, children and a breast biopsy.

•Uptake is clearly informed by lifetime risk of BC and higher in younger the women.


Bilateral-Risk-Reducing-Mastectomy-(BRRM) is well described in BRCA1/2 pathogenic variant carriers. However, little is known about the relative uptake, time trends or factors influencing uptake in those at increased breast cancer risk not known to be carriers. The aim of this study is to assess these factors in both groups.


BRRM uptake was assessed from entry to the Manchester Family History Clinic or from date of personal BRCA1/2 test. Follow up was censored at BRRM, breast cancer diagnosis, death or January 01, 2020. Cumulative incidence and cause specific and competing risk regression analyses were used to assess the significance of factors associated with BRRM.


Of 7195 women at ≥25% lifetime breast cancer risk followed for up to 32 years, 451 (6.2%) underwent pre-symptomatic BRRM. Of those eligible in different risk groups the 20-year uptake of BRRM was 47.7%-(95%CI = 42.4–53.2%) in 479 BRCA1/2 carriers; 9.0% (95%CI = 7.26–11.24%) in 1261 women at ≥40% lifetime risk (non-BRCA), 4.8%-(95%CI = 3.98–5.73%) in 3561 women at 30–39% risk and 2.9%-(95%CI = 2.09–4.09%) in 1783 women at 25–29% lifetime risk. In cause-specific Cox regression analysis death of a sister with breast cancer<50 (OR = 2.4; 95%CI = 1.7–3.4), mother<60 (OR = 1.9; 95%CI = 1.5–2.3), having children (OR = 1.4; 95%CI = 1.1–1.8), breast biopsy (OR = 1.4; 95%CI = 1.0–1.8) were all independently associated with BRRM uptake, while being older at assessment was less likely to be associated with BRRM (>50; OR = 0.26,95%CI = 0.17–0.41). Uptake continued to rise to 20 years from initial risk assessment.


We have identified several additional factors that correlate with BRRM uptake and demonstrate continued increases over time. These factors will help to tailor counselling and support for women.



Information needs on breast cancer genetic and non-genetic risk factors in relatives of women with a BRCA1/2 or PALB2 pathogenic variant


by Anne Brédart, Antoine De Pauw, Amélie Anota, Anja Tüchler, Julia Dick, Anita Müller, Jean-Luc Kop, Kerstin Rhiem, Rita Schmutzler, Peter Devilee, Dominique Stoppa-Lyonnet, Sylvie Dolbeault 


The Breast: August 23, 2021



Comprehensive breast cancer (BC) risk models integrating effects of genetic (GRF) and non-genetic risk factors (NGRF) may refine BC prevention recommendations. We explored the perceived information received on BC risk factors, and related characteristics, in female relatives of women with a BRCA1/2 or PALB2 pathogenic variant, undergoing BC risk assessment using the CanRisk© prediction tool.


Of 200 consecutive cancer-free women approached after the initial genetic consultation, 161 (80.5%) filled in questionnaires on their perception of information received and wished further information on BC risk factors (e.g., being a carrier of a moderate risk altered gene, personal genetic profile, lifestyles). Multilevel multivariate linear models were performed accounting for the clinician who met the counselee and exploring the effect of counselees’ socio-demographic, familial and psychological characteristics on the perceived extent of information received.


Perceived no/little information received and wish for further information were more frequent for NGRF (>50%) than for GRF, especially high-risk genes (<20%). Perceived amount of information received and desire for further information were inversely correlated (p=<0.0001). Higher education level related to lower perceived levels of information received on GRF. Younger counselees' age (β = 0.13, p = 0.02) and less frequent engagement coping (e.g., inclination to solicit information) (β = 0.24, p = 0.02) related to lower perceived information received about NGRF. Other assessed counselees’ features were not found to be associated to GRF and NGRF information perception.


Awareness of counselees’ perceived lack of information on BC risk factors indicates a need to enhance evidence-based information on BC NGRF especially.


Evidence-based tailored nutrition educational intervention improves adherence to dietary guidelines, anthropometric measures and serum metabolic biomarkers in early-stage breast cancer patients: A prospective interventional study

by Ilaria Trestini, Isabella Sperduti, Alberto Caldart, Clelia Bonaiuto, Elena Fiorio, Veronica Parolin, Valentina Zambonin, Sara Zanelli, Daniela Tregnago, Alice Avancini, Marco Cintoni, Sara Pilotto, Maria Cristina Mele, Antonio Gasbarrini, Giovanni Scambia, Michele Milella, Giampaolo Tortora, Emilio Bria, Luisa Carbognin 


The Breast: August 21, 2021



The impact of the adherence to dietary guidelines of early-stage breast cancer (EBC) patients on body composition changes during treatment is not entirely defined. This study aimed to evaluate the role of an evidence-based nutrition educational intervention, according to adherence to dietary guidelines, in EBC patients.


This prospective study included EBC patients, candidates for neoadjuvant/adjuvant therapy. Patients received an evidence-based tailored nutrition educational intervention. The adherence to dietary guidelines, anthropometric and dietary assessments, and blood glucose and lipid profile tests were evaluated at baseline and after a 12-months nutritional intervention.


Two hundred and forty-three patients were enrolled. At baseline, 38.3% and 23.9% of patients were overweight and obese, weight gain ≥5% (compared to 6-months before enrollment) and central obesity were observed in 47.3% and 52.7% of patients, respectively. Adherence to dietary guidelines was low (median Med-Diet score: 6 [IQR 4–8]). After the nutritional intervention (median follow-up: 22 months [range 12–45]), adherence to dietary guidelines significantly increased (median Med-Diet score: 12 [IQR 8–13]), p < 0.0001). High adherence to dietary guidelines (defines as Med-Diet score ≥10) significantly correlated with: 1) overall weight loss ≥5% (21.8% vs. 2.5%, p = 0.003); 2) median BMI drop (from 25.6 kg/m2 to 24.4 kg/m2, p = 0.003); 3) lower prevalence of central obesity (38.2% vs. 7.2%, p = 0.01); 4) improvement in blood glucose levels and lipid profile.


This study suggests that an evidence-based tailored nutrition educational intervention during treatment for EBC significantly increases overall adherence to dietary guidelines, and it improves both anthropometric measures and serum metabolic biomarkers in patients with high adherence.


Positive effects of the enhanced recovery after surgery (ERAS) protocol in DIEP flap breast reconstruction


by N. Gort, B.G.I. van Gaal, H.J.P. Tielemans, D.J.O. Ulrich, S. Hummelink 


The Breast: August 19, 2021



Enhanced recovery after surgery protocols are successfully implemented in different surgical specialties, but a specific protocol for autologous breast reconstruction is missing. The aim of this study was to determine whether an enhanced recovery after surgery (ERAS) protocol contributes to a reduced length of stay without an increase in postoperative complications for patients undergoing a DIEP flap breast reconstruction.

Materials en methods

The effect of the ERAS protocol was examined using a single-center patient-control study comparing two groups of patients. Patients who underwent surgery between November 2017 and November 2018 using the ERAS protocol were compared with a historical control group (pre-ERAS) who underwent surgery between November 2016 and November 2017. The primary outcome measure was hospital length of stay. Secondary outcome measures were postoperative pain and postoperative complications.


152 patients were included (ERAS group, n = 73; control group, n = 79). Mean hospital length of stay was significantly shorter in the ERAS group than in the control group (5 vs. 6 days, p < 0.001). The average pain score was 1.73 in de the ERAS group compared to 2.17 in the control group (p = 0.032). There were no significant differences between the groups in postoperative complications. The ERAS group experienced less constipation (41 vs. 25 patients, p = 0.028).


An enhanced recovery after surgery protocol contributes an accelerated postoperative recovery of patients undergoing a DIEP flap breast reconstruction. In this study a significant decrease was found in hospital length of stay, patient-reported pain score and adverse health issues.




Targeting ADCC: A different approach to HER2 breast cancer in the immunotherapy era


by Pablo Mandó, Sergio G. Rivero, Manglio M. Rizzo, Marina Pinkasz, Estrella M. Levy 


The Breast: August 19, 2021


The clinical outcome of patients with human epidermal growth factor receptor 2 (HER2) amplified breast carcinoma (BC) has improved with the development of anti-HER2 targeted therapies. However, patients can experience disease recurrence after curative intent and disease progression in the metastatic setting. In the current era of evolving immunotherapy agents, the understanding of the immune response against HER2 tumor cells developed by anti-HER2 antibodies (Abs) is rapidly evolving. Trastuzumab therapy promotes Natural Killer (NK) cell activation in patients with BC overexpressing HER2, indicating that the efficacy of short-term trastuzumab monotherapy, albeit direct inhibition of HER, could also be related with antibody-dependent cell-mediated cytotoxicity (ADCC).


Population-based recurrence rates among older women with HR-positive, HER2-negative early breast cancer: Clinical risk factors, frailty status, and differences by race


by Jifang Zhou, Jenilee Cueto, Naomi Y. Ko, Kent F. Hoskins, Nadia A. Nabulsi, Alemseged A. Asfaw, Colin C. Hubbard, Debanjali Mitra, Gregory S. Calip, Ernest H. Law 


The Breast:  VOLUME 59, P367-375, OCTOBER 01, 2021



Multiple independent risk factors are associated with the prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC), the most common BC subtype. This study describes U.S. population-based recurrence rates among older, resected women with HR+/HER2- early BC.


We conducted a retrospective cohort study of older women diagnosed with incident, invasive stages I-III HR+/HER2- BC who underwent surgery to remove the primary tumor using the Surveillance, Epidemiology, and End Results (SEER)-Medicare Linked Database (2007–2015). SEER records and administrative health claims data were used to ascertain patient and tumor-specific characteristics, treatment, and frailty status. Cumulative incidences of BC recurrence were estimated using a validated algorithm for administrative claims data. Multivariable Fine-Gray competing risk models estimated adjusted subdistribution hazards ratios and 95 % confidence intervals for associations with BC recurrence risk.


Overall, 46,027 women age ≥65 years were included in our analysis. Over a median follow up of 7 years, 6531 women experienced BC recurrence with an estimated 3 and 5-year cumulative incidence rates of 10 % and 16 %, respectively. Higher 3- and 5-year cumulative incidences were observed in women with larger tumor size (5+ cm, 21 % and 28 %), lymph node involvement (4+ nodes, 27 % and 37 %), and with frail health status at diagnosis (13 % and 20 %). Independent of these clinical risk factors, Black, Hispanic and American Indian/Alaskan Native women had significantly increased BC recurrence risks.


Rates of recurrence in HR+/HER2- early BC differs by several patient and clinical factors, including high-risk tumor characteristics. Racial differences in BC outcomes deserve continued attention from clinicians and policymakers.


Nerve Coaptation Improves the Sensory Recovery of the Breast in DIEP Flap Breast Reconstruction


by Beugels, Jop; Bijkerk, Ennie; Lataster, Arno; Heuts, Esther M.; van der Hulst, René R. W. J.; Tuinder, Stefania M. H. 


Plastic and Reconstructive Surgery: August 2021 - Volume 148 - Issue 2 - p 273-284


Background: Restoring the sensation of the reconstructed breast has increasingly become a goal of autologous breast reconstruction. The aim of this study was to analyze the sensory recovery of the breast and donor site of innervated compared to noninnervated deep inferior epigastric perforator (DIEP) flap breast reconstructions, to assess associated factors, and to compare the differences between preoperative and postoperative sensation.

Methods: A prospective cohort study was conducted, including patients who underwent innervated or noninnervated DIEP flap breast reconstruction between August of 2016 and August of 2018. Nerve coaptation was performed to the anterior cutaneous branch of the third intercostal nerve. Preoperative and postoperative sensory testing of the breast and donor site was performed with Semmes-Weinstein monofilaments.

Results: A total of 67 patients with 94 innervated DIEP flaps and 58 patients with 80 noninnervated DIEP flaps were included. Nerve coaptation was significantly associated with lower mean monofilament values for the breast (−0.48; p < 0.001), whereas no significant differences were found for the donor site (−0.16; p = 0.161) of innervated compared to noninnervated DIEP flaps. Factors positively or negatively associated with sensory recovery of the breast and donor site were identified. Preoperative versus postoperative comparison demonstrated significantly superior sensory recovery of the breast in innervated flaps (adjusted difference, −0.48; p = 0.017).

Conclusions: This study demonstrated that nerve coaptation in DIEP flap breast reconstruction significantly improved the sensory recovery of the breast compared to noninnervated flaps. The sensory recovery of the donor site was not compromised in innervated reconstructions. The results support the role of nerve coaptation in autologous breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Thursday, 22 July 2021

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



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.


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).


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 %).


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



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.


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.


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.


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.