Polygenic risk scores and breast cancer risk prediction

 

by Eleanor Roberts, Sacha Howell, Gareth Evans 

 

The Breast: VOLUME 67, P71-77, FEBRUARY 2023

 

Abstract

Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have the potential to improve screening and prevention strategies. PRS combine the risk from Single nucleotide polymorphisms (SNPs) associated with breast cancer in Genome Wide Association Studies (GWAS) and explain over 30% of breast cancer heritability. When incorporated into risk models, the more personalised risk assessment derived from PRS, help identify women at higher risk of breast cancer development and enables the implementation of stratified screening and prevention approaches. This review describes the role of PRS in breast cancer risk prediction including the development of PRS and their clinical application. We have also examined the role of PRS within more well-established risk prediction models which incorporate known classic risk factors and discuss the interaction of PRS with these factors and their capacity to predict breast cancer subtypes. Before PRS can be implemented on a population-wide scale, there are several challenges that must be addressed. Perhaps the most pressing of these is the use of PRS in women of non-White European origin, where PRS have been shown to have attenuated risk prediction both in discrimination and calibration. We discuss progress in developing and applying PRS in non-white European populations. PRS represent a significant advance in breast cancer risk prediction and their further development will undoubtedly enhance personalisation.

Prepectoral Direct-to-Implant Breast Reconstruction: Safety Outcome Endpoints and Delineation of Risk Factors

Prepectoral Direct-to-Implant Breast Reconstruction: Safety Outcome Endpoints and Delineation of Risk Factors

by Nealon, Kassandra P.; Weitzman, Rachel E.; Sobti, Nikhil; Gadd, Michele; Specht, Michelle; Jimenez, Rachel B.; Ehrlichman, Richard; Faulkner, Heather R.; Austen, William G. Jr; Liao, Eric C.

Plastic and Reconstructive Surgery: May 2020 - Volume 145 - Issue 5 - p 898e-908e

Background: Continued evolution of implant-based breast reconstruction involves immediate placement of the implant above the pectoralis muscle. The shift to prepectoral breast reconstruction is driven by goals of decreasing morbidity such as breast animation deformity, range-of-motion problems, and pain, and is made possible by improvements in mastectomy skin flap viability. To define clinical factors to guide patient selection for direct-to-implant prepectoral implant reconstruction, this study compares safety endpoints and risk factors between prepectoral and subpectoral direct-to-implant breast reconstruction cohorts. The authors hypothesized that prepectoral direct-to-implant breast reconstruction is a safe alternative to subpectoral direct-to-implant breast reconstruction.

Methods: Retrospective chart review identified patients who underwent prepectoral and subpectoral direct-to-implant breast reconstruction, performed by a team of five surgical oncologists and two plastic surgeons. Univariate analysis compared patient characteristics between cohorts. A penalized logistic regression model was constructed to identify relationships between postoperative complications and covariate risk factors.

Results: A cohort of 114 prepectoral direct-to-implant patients was compared with 142 subpectoral direct-to-implant patients. The results of the penalized regression model demonstrated equivalence in safety metrics between prepectoral direct-to-implant and subpectoral direct-to-implant breast reconstruction, including seroma (p = 0.0883), cancer recurrence (p = 0.876), explantation (p = 0.992), capsular contracture (p = 0.158), mastectomy skin flap necrosis (p = 0.769), infection (p = 0.523), hematoma (p = 0.228), and revision (p = 0.122).

Conclusions: This study demonstrates that prepectoral direct-to-implant reconstruction is a safe alternative to subpectoral direct-to-implant reconstruction. Given the low morbidity and elimination of animation deformity, prepectoral direct-to-implant reconstruction should be considered when the mastectomy skin flap is robust. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Tackling the diversity of breast cancer related lymphedema: Perspectives on diagnosis, risk assessment, and clinical management

Tackling the diversity of breast cancer related lymphedema: Perspectives on diagnosis, risk assessment, and clinical management

by Anna Michelotti, Marco Invernizzi, Gianluca Lopez, Daniele Lorenzini, Francesco Nesa, Alessandro De Sire, Nicola Fusco  

The Breast: April 2019, Volume 44, Pages 15-23

Breast cancer related lymphedema (BCRL) develops as a consequence of surgical treatment and/or radiation therapy in a significant number of breast cancer patients. The etiology of this condition is multifactorial and has not yet been completely elucidated. Risk factors include high body mass index, radical surgical procedures (i.e. mastectomy and axillary lymph node dissection), number of lymph nodes removed and number of metastatic lymph nodes, as well as nodal radiation, and chemotherapy. However, these predisposing factors explain only partially the BCRL occurrence, suggesting the possible involvement of individual determinants.

Estimation of the benefit and harms of including clinical breast examination in an organized breast screening program

Estimation of the benefit and harms of including clinical breast examination in an organized breast screening program

 by Huan Jiang, Stephen D. Walter, Patrick Brown, Parminder Raina, Anna M. Chiarelli

The Breast: February 2019, Volume 43, Pages 105-112

There is controversy about the value of clinical breast examination (CBE) in addition to mammography for breast screening. The study investigates the associations between risk factors such as mammographic density, hormone therapy use and family history and the effectiveness of screening mammography with or without CBE.

Novel Approach for Risk-Reducing Mastectomy: First-Stage Implant Placement and Subsequent Second-Stage Mastectomy

Novel Approach for Risk-Reducing Mastectomy: First-Stage Implant Placement and Subsequent Second-Stage Mastectomy

 by Lim, Geok Hoon; Baildam, Andrew D.  

Plastic and Reconstructive Surgery: September 2018 - Volume 142 - Issue 3 - p 607–610

Background: Risk-reducing mastectomy with tissue expander and then implant-based breast reconstruction conventionally involved immediate submuscular placement of tissue expanders during mastectomy and then, after expansion, replacement of expanders for permanent implants in a second-stage operation. Use of acellular dermal matrix can achieve a single-stage operation; however, acellular dermal matrices are costly and may have potential complications. The authors aim to assess the feasibility of placement of implants as a first-stage procedure before risk-reducing mastectomy as a novel technique of reconstruction that avoids the need for serial outpatient expansion and acellular dermal matrix.

Methods: Patients for whom risk-reducing mastectomy was planned were offered first-stage dual-plane placement of fixed volume silicone gel permanent implants by means of inframammary fold incisions. Risk-reducing mastectomy was undertaken several months later as the second operation, leaving the implants in place protected by the muscle and capsule pocket. Nipples were preserved or reconstructed according to the patient’s choice.

Results: Eight patients with 15 operated breasts were recruited. Anatomically shaped implants were used in all patients, and complete coverage of each implant was achieved. Mean implant volume was 433 ml (range, 290 to 545 ml). There were no complications, and good aesthetic outcomes were achieved.

Conclusions: This proof-of-principle study finds that placement of implants before risk-reducing mastectomy is a novel technique for women at high breast cancer risk that could reduce the use of tissue expanders and acellular dermal matrices and their associated problems. Two-stage risk-reducing mastectomy with first-stage implant placement and subsequent risk-reducing mastectomy leaving the implants in place is feasible, with no complications, and can produce a good cosmetic outcome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Acellular Dermal Matrix in Immediate Expander/Implant Breast Reconstruction: A Multicenter Assessment of Risks and Benefits

Acellular Dermal Matrix in Immediate Expander/Implant Breast Reconstruction: A Multicenter Assessment of Risks and Benefits

Sorkin M et al

Plastic and Reconstructive Surgery: December 2017 - Volume 140 - Issue 6 - p 1091–1100

Background: Acellular dermal matrix has gained widespread acceptance in immediate expander/implant reconstruction because of perceived benefits, including improved expansion dynamics and superior aesthetic results. Although previous investigators have evaluated its risks, few studies have assessed the impact of acellular dermal matrix on other outcomes, including patient-reported measures. Methods: The Mastectomy Reconstruction Outcomes Consortium Study used a prospective cohort design to evaluate patients undergoing postmastectomy reconstruction from 10 centers and 58 participating surgeons between 2012 and 2015. The analysis focused on women undergoing immediate tissue expander reconstruction following mastectomies for cancer treatment or prophylaxis. Medical records and patient-reported outcome data, using the BREAST-Q and Numeric Pain Rating Scale instruments, were reviewed. Bivariate analyses and mixed-effects regression models were applied. Results: A total of 1297 patients were evaluated, including 655 (50.5 percent) with acellular dermal matrix and 642 (49.5 percent) without acellular dermal matrix. Controlling for demographic and clinical covariates, no significant differences were seen between acellular dermal matrix and non–acellular dermal matrix cohorts in overall complications (OR, 1.21; p = 0.263), major complications (OR, 1.43; p = 0.052), wound infections (OR, 1.49; p = 0.118), or reconstructive failures (OR, 1.55; p = 0.089) at 2 years after reconstruction. There were also no significant differences between the cohorts in the time to expander/implant exchange (p = 0.78). No significant differences were observed in patient-reported outcome scores, including satisfaction with breasts, psychosocial well-being, sexual well-being, physical well-being, and postoperative pain. Conclusions: In this multicenter, prospective analysis, the authors found no significant acellular dermal matrix effects on complications, time to exchange, or patient-reported outcome in immediate expander/implant breast reconstruction. Further studies are needed to develop criteria for more selective use of acellular dermal matrix in these patients.

Low risk of recurrence in elderly patients treated with breast conserving therapy in a single institute

Low risk of recurrence in elderly patients treated with breast conserving therapy in a single institute

The Breast December 2016 Volume 30,  Pages 19- 25

van der LeijF et al

To guide decision making in preventing over- or under-treatment in older breast cancer patients who have undergone breast conserving surgery, we analyzed prognostic factors and risk of recurrence in a consecutive series of patients ≥ 65 years old with breast cancer and identified subgroups that may benefit or not from more intensive treatment.