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

 

Background: 

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.

Methods: 

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.

Results: 

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.

Conclusions: 

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

 

Background

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).

Results

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.

Conclusion

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

 

Aim

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.

Methods

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.

Results

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.

Conclusion

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

 

 Background

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.

Methods

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).

Results

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]).

Conclusions

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

 

Highlights

•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.

Abstract

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

 

Background

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.

Methods

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.

Results

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.

Conclusion

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

 

Background

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.

Methods

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.gov, NCT01064635.

Findings

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.

Interpretation

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.