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.

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

 Highlights

• 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

Highlights

•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.

Background

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.

Methods

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.

Results

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.

Conclusion

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

 

Objectives

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.

Methods

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.

Results

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.

Conclusions

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

 

Purpose

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.

Methods

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.

Results

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.

Conclusion

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

 

Background

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.

Results

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).

Conclusion

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

 

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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.