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Studies conducted among women in the general population suggest that various anthropometric measures, including height and weight, may be associated with the risk of developing ovarian cancer. Whether such an association exists among women who carry a BRCA1 or BRCA2 mutation has not been evaluated. Thus, we investigated the association between height, weight, changes in body weight, and BMI, and the risk of developing ovarian cancer among 938 women carrying a BRCA1 or BRCA2 mutation. A matched case-control study was conducted in 469 pairs of women carrying a deleterious mutation in either BRCA1 (n = 403 pairs) or BRCA2 (n = 66 pairs). Information about height and weight at ages 18, 30, and 40 was collected from a questionnaire routinely administered to women during the course of genetic counseling. Conditional logistic regression was used to estimate the association between these body size measures and the risk of ovarian cancer. Height, weight, and BMI were not associated with the risk of ovarian cancer (P-trend ≥0.15). Also, there was no association between changes in body weight between ages 18-30, or ages 30-40, or ages 18-40 and the risk of ovarian cancer (P-trend ≥0.28). The results from this study suggest that height, weight, or weight gain do not influence the risk of ovarian cancer among carriers of a BRCA1 or BRCA2 mutation. [ABSTRACT FROM AUTHOR]

Whether or not women who harbor a germline pathogenic variant ('mutation') in the BRCA1 or BRCA2 genes are at elevated risk of developing endometrial cancer is yet to be determined. We conducted a prospective analysis of 4959 BRCA mutation carriers with no prior history of cancer (except for breast or melanoma) and an intact uterus. After a mean of 6.7 years of follow-up there were 38 incident cases of endometrial cancer diagnosed; 30 among BRCA1 carriers and eight among BRCA2 carriers. The mean age at diagnosis was 58.4 years (range 46.8–76.1). The majority were of the endometrioid subtype (n = 16), followed by mixed endometroid and serous (n = 4), serous (n = 3) or clear cell (n = 1) (missing = 13). The cumulative incidence from age 40 to age 70 was 3.4% for BRCA1 carriers and was 1.6% for BRCA2 mutation carriers. Prior tamoxifen use was associated with a significant two–fold increased risk (HR = 2.24; 95% CI 1.10–4.55). There was no significant association between exogenous hormone use, oophorectomy, smoking or BMI at age 40 and risk (P ≥ 0.32). Compared to the general population, we observed higher rates of endometrial cancer among young BRCA1 mutation carriers; however, lifetime risks were similar. Women with prior tamoxifen exposure were at a significantly increased risk. These findings were based. on a small number of incident cases and require confirmation with additional follow-up of our aging cohort. • We prospectively evaluated whether endometrial cancer is part of the BRCA - spectrum. • Cumulative incidence was 3.4% for BRCA1 and 1.6% for BRCA2 mutation carriers. • Tamoxifen use was a significant risk factor BRCA -endometrial cancer. • With few incident cases, we are not able to conclusively confirm an increased risk. • Hysterectomy at the time of preventive ophorectomy should be individualized. [ABSTRACT FROM AUTHOR]

Despite consensus guidelines, most patients with early-stage triple-negative (TN) and HER2-positive (HER2+) breast cancer do not see a medical oncologist prior to surgery and do not receive neoadjuvant chemotherapy (NAC). To understand barriers to care, we aimed to characterize the relationship between geography (region of residence and cancer centre proximity) and receipt of a pre-treatment medical oncology consultation and NAC for patients with TN and HER2+ breast cancer. Using linked administrative datasets in Ontario, Canada, we performed a retrospective population-based analysis of women diagnosed with stage I–III TN or HER2+ breast cancer from 2012 to 2020. The outcomes were a pre-treatment medical oncology consultation and the initiation of NAC. We created choropleth maps to assess the distribution of the outcomes and cancer centres across census divisions. To assess the relationship between distance to the nearest cancer centre and outcomes, we performed multivariable regression analyses adjusted for relevant factors, including tumour extent and nodal status. Of 14,647 patients, 29.9% received a pre-treatment medical oncology consultation and 77.7% received NAC. Mapping demonstrated high interregional variability, ranging across census divisions from 12.5% to 64.3% for medical oncology consultation and from 8.8% to 64.3% for NAC. In the full cohort, compared to a distance of ≤5 km from the nearest cancer centre, only 10–25 km was significantly associated with lower odds of NAC (OR 0.83, 95% CI 0.70–0.99). Greater distances were not associated with pre-treatment medical oncology consultation. The interregional variability in medical oncology consultation and NAC for patients with TN and HER2+ breast cancer suggests that regional and/or provider practice patterns underlie discrepancies in the referral for and receipt of NAC. These findings can inform interventions to improve equitable access to NAC for eligible patients. [ABSTRACT FROM AUTHOR]

The hydrophobicity of six strains representing three species of Lactobacillus was measured using dextran-polyethylene glycol contact angle measurements. These ranged from 123.6° for Lactobacillus casei douche to 26.2° for L. casei RC-17 under identical growth conditions. The results indicated that the nutritional environment affected bacterial hydrophobicity. Electrophoretic mobilities of the lactobacilli were also determined and found to be negative for all specimens, and to vary with growth media, especially when sugars were added to urine. The electrophoretic mobility histograms showed one main peak for all strains, except Lactobacillus acidophilus T-13 which had two peaks, suggesting two morphological sizes or types within its population. In addition, strain T-13 was more positively charged than the other five strains after growth in agar, urine, and supplemented urine. The use of contact angle and electrophoretic mobility techniques allows examination of cell surface properties of lactobacilli that may have importance in the colonization of mucosal epithelia. [ABSTRACT FROM AUTHOR]

Background: Approximately 75% of breast cancer (BC) is associated with luminal differentiation expressing endocrine receptors (ER). For ER+ HER2− tumors, adjuvant endocrine therapy (ET) is the cornerstone treatment. Although relapse events steadily continue, the ET benefits translate to dramatically lengthen life expectancy with bearable side-effects. This review of ER+ HER2− female BC outlines suitable adjuvant treatment strategies to help guide clinical decision making around appropriate therapy. Methods: A literature search was conducted in Embase, Medline, and the Cochrane Libraries, using ER+ HER−, ET BC keywords. Results: In low-risk patients: five years of ET is the standard option. While Tamoxifen remains the preferred selection for premenopausal women, AI is the choice for postmenopausal patients. In the high-risk category: ET plus/minus OFS with two years of Abemaciclib is recommended. Although extended ET for a total of ten years is an alternative, the optimal AI duration is undetermined; nevertheless an additional two to three years beyond the initial five years may be sufficient. In this postmenopausal group, bisphosphonate is endorsed. Conclusions: Classifying the risk category assists in deciding the treatment route and its optimal duration. Tailoring the breadth of ET hinges on a wide array of factors to be appraised for each individualized case, including weighing its benefits and harms. [ABSTRACT FROM AUTHOR]

Objective: The American Society of Clinical Oncology recommends all patients with high‐grade serous ovarian carcinoma (HGSC) undergo germline genetic testing. Genetic consultation rates in Ontario, Canada, only reached 13.3% in 2011. In 2016, PARP inhibitor maintenance therapy became available in Ontario for BRCA‐positive HGSC patients. Given expanding treatment options, we re‐examined genetic consultation rates among HGSC patients. Methods: This retrospective cohort study identified patients diagnosed with HGSC between 2012 and 2019 using population‐based administrative data from Ontario. Genetics consultations were identified using Ontario Health Insurance Plan billing codes. Consultation rates over time were analyzed using Cochran–Armitage trend test and segmental regression analysis. Multivariable analysis identified factors associated with attending genetics consultation. Results: This study included 4645 HGSC patients. The mean age was 64.2 years (±SD 12.3); 56.3% had stage 3–4 disease. Overall, approximately 35% attended genetics consultations. The genetic consultation rate per year increased significantly from 21.6% to 42.6% (P < 0.001). Shorter times between diagnosis and genetics consult were observed after PARP inhibitors became available (68.1 vs 34.1 weeks, P < 0.001). Patients treated at designated cancer centers (odds ratio [OR] 2.11, P < 0.001), diagnosed in later years (OR 1.33, P < 0.001), and from higher income groups (P < 0.05) were more likely to attend genetics consultation; older patients were less likely (OR 0.98, P < 0.001). After PARP inhibitors became available, consultation rates plateaued (P < 0.001). Conclusions: Between 2012 and 2019, genetic consultation rates improved significantly among HGSC patients; however, a large proportion of patients never attended consultation. Further exploration of barriers to care is warranted to improve consultation rates and ensure equitable access to care. Synopsis: Genetic consultation rates improved significantly among ovarian HGSC patients from 2012 to 2019; however, overall consultation rates remained suboptimal. Barriers to care persist despite publicly insured services. [ABSTRACT FROM AUTHOR]

Simple Summary: The current approach to breast cancer screening, which is based on a person's age, overlooks individual-level differences in breast cancer risk. As a result, many people are over- or under-screened according to their actual risk of breast cancer. Risk-stratified breast screening may overcome the limitations of age-based screening, but there are still many knowledge gaps regarding how best to implement it in the population setting. This study will generate the first Canadian evidence on the adoption of breast cancer risk assessment in the population setting, to support the future implementation of risk-stratified breast cancer screening. This study demonstrated that, while risk assessment for risk-stratified screening at the population level is feasible, an equity lens must be considered in implementation to ensure cancer-screening disparities are not widened. Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40–69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened. [ABSTRACT FROM AUTHOR]

Background: It has not been clearly established if skin cancer or melanoma are manifestations of BRCA1 or BRCA2 mutation carrier status. Estimating the risk of skin cancer is an important step towards developing screening recommendations. Methods: We report the findings of a prospective cohort study of 6,207 women from North America who carry BRCA1 or BRCA2 mutations. Women were followed from the date of baseline questionnaire to the diagnosis of skin cancer, to age 80 years, death from any cause, or the date of last follow-up. Results: During the mean follow-up period of eight years, 3.7% of women with a BRCA1 mutation (133 of 3,623) and 3.8% of women with a BRCA2 mutation (99 of 2,584) reported a diagnosis of skin cancer (including both keratinocyte carcinomas and melanoma). The cumulative risk of all types of skin cancer from age 20 to 80 years was 14.1% for BRCA1 carriers and 10.7% for BRCA2 carriers. The cumulative risk of melanoma was 2.5% for BRCA1 carriers and 2.3% for BRCA2 carriers, compared to 1.5% for women in the general population in the United States. The strongest risk factor for skin cancer was a prior diagnosis of skin cancer. Conclusion: The risk of non-melanoma skin cancer in women who carry a mutation in BRCA1 or BRCA2 is similar to that of non-carrier women. The risk of melanoma appears to be slightly elevated. We suggest that a referral to a dermatologist or primary care provider for BRCA mutation carriers for annual skin examination and counselling regarding limiting UV exposure, the use of sunscreen and recognizing the early signs of melanoma might be warranted, but further studies are necessary. [ABSTRACT FROM AUTHOR]

Background: Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation.Methods: We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates.Results: Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm2 vs. 53.1cm2; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant.Conclusions: In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models. [ABSTRACT FROM AUTHOR]

Background: Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer. Methods: This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan–Meier methods and Cox proportional hazards regression. Propensity score matching was applied. Results: From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74–0.98, p-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test p = 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72–2.30, p-value = 0.39) did not significantly differ between treatment groups. Conclusions: Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments. [ABSTRACT FROM AUTHOR]

Background: Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. Methods: Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. Results: There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05–1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. Conclusions: In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated impact of contralateral mastectomy on survival of women with breast cancer (BRCA) gene mutations. It explores mortality between women who have undergone preventive mastectomy and those who were treated with unilateral mastectomy. Topics addressed also include reducing breast cancer risks through mastectomy, selection and clinical assessment of study participants, research duration, and generalisability to women with sporadic breast cancer.

Background: The use of preoperative breast magnetic resonance imaging (MRI) after the diagnosis of breast cancer by mammography and/or ultrasound is inconsistent. Methods: After conducting a systematic review and meta-analysis comparing preoperative breast MRI versus no MRI, we reconvened to prepare a clinical practice guideline on this topic. Results: Based on the evidence that MRI improved recurrence, decreased the rates of reoperations (re-excisions or conversion mastectomy), and increased detection of synchronous contralateral breast cancer, we recommend that preoperative breast MRI should be considered on a case-by-case basis in patients diagnosed with breast cancer for whom additional information about disease extent could influence treatment. Based on stronger evidence, preoperative breast MRI is recommended in patients diagnosed with invasive lobular carcinoma for whom additional information about disease extent could influence treatment. For both recommendations, the decision to proceed with MRI would be conditional on shared decision-making between care providers and the patient, taking into account the benefits and risks of MRI as well as patient preferences. Based on the opinion of the Working Group, preoperative breast MRI is also recommended in the following more specific situations: (a) to aid in surgical planning of breast conserving surgery in patients with suspected or known multicentric or multifocal disease; (b) to identify additional lesions in patients with dense breasts; (c) to determine the presence of pectoralis major muscle/chest wall invasion in patients with posteriorly located tumours or when invasion of the pectoralis major muscle or chest wall is suspected; (d) to aid in surgical planning for skin/nipple-sparing mastectomies, autologous reconstruction, oncoplastic surgery, and breast conserving surgery with suspected nipple/areolar involvement; and (e) in patients with familial/hereditary breast cancer but who have not had recent breast MRI as part of screening or diagnosis. [ABSTRACT FROM AUTHOR]

We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG's recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to estimate the cumulative risks of all cancers in women from 50 to 75 years of age with a BRCA1 or BRCA2 pathogenic variant. Methods: Participants were women with BRCA1 or BRCA2 pathogenic variants from 85 centers in 16 countries. Women were eligible if they had no cancer before the age of 50 years. Participants completed a baseline questionnaire and follow‐up questionnaires every 2 years. Women were followed from age 50 until a diagnosis of cancer, death, age 75, or last follow‐up. The risk of all cancers combined from age 50 to 75 was estimated using the Kaplan–Meier method. Results: There were 2211 women included (1470 BRCA1 and 742 BRCA2). There were 379 cancers diagnosed in the cohort between 50 and 75 years. The actuarial risk of any cancer from age 50 to 75 was 49% for BRCA1 and 43% for BRCA2. Breast (n = 186) and ovarian (n = 45) were the most frequent cancers observed. For women who had both risk‐reducing mastectomy and bilateral salpingo‐oophorectomy before age 50, the risk of developing any cancer between age 50 and 75 was 9%. Conclusion: Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer between the ages of 50 and 75 years and should be counselled appropriately. Women with a BRCA1 or BRCA2 pathogenic variant have a high risk of cancer after age 50 and should be counseled appropriately. [ABSTRACT FROM AUTHOR]

Introduction: Breastfeeding has been inversely related to breast cancer risk in the general population. Clarifying the role of breastfeeding among women with a BRCA1 or BRCA2 mutation may be helpful for risk assessment and for recommendations regarding prevention. We present an updated analysis of breastfeeding and risk of breast cancer using a large matched sample of BRCA mutation carriers.Methods: We conducted a case-control study of 1,665 pairs of women with a deleterious mutation in either BRCA1 (n = 1,243 pairs) or BRCA2 (n = 422 pairs). Breast cancer cases and unaffected controls were matched on year of birth, mutation status, country of residence and parity. Information about reproductive factors, including breastfeeding for each live birth, was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the association between ever having breastfed, as well as total duration of breastfeeding, and the risk of breast cancer.Results: Among BRCA1 mutation carriers, breastfeeding for at least one year was associated with a 32% reduction in risk (OR = 0.68; 95% CI 0.52 to 0.91; P = 0.008); breastfeeding for two or more years conferred a greater reduction in risk (OR = 0.51; 95% CI 0.35 to 0.74). Among BRCA2 mutation carriers, there was no significant association between breastfeeding for at least one year and breast cancer risk (OR = 0.83; 95% CI 0.53 to 1.31; P = 0.43).Conclusions: These data extend our previous findings that breastfeeding protects against BRCA1-, but not BRCA2-associated breast cancer. BRCA mutation carriers should be advised of the benefit of breastfeeding in terms of reducing breast cancer risk. [ABSTRACT FROM AUTHOR]

The article comments on the use of prophylactic mastectomy for women with BRCA1 and BRCA2 mutations. According to the author, the efficacy of tamoxifen in treating women with a BRCA1 mutation has been examined because 80 percent of breast tumors arising in the patients do not express estrogen receptors.

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results. [ABSTRACT FROM AUTHOR]

The article discusses the problems with genetic susceptibility testing for breast cancer. Some women who receive test results indicating that they have a higher family risk for breast cancer undergo radical mastectomies in an effort to prevent the disease. The article argues that there is insufficient evidence that women from families who carry BRCA1 or BRCA2 mutations, which indicate a higher risk, may not have had increased risk for breast cancer. The article claims that though radical preventive mastectomy does reduce predicted breast cancer risk, it is at the unnecessary cost of disfiguring surgery and psychological trauma.

Breast cancer recurrence is an important outcome for patients and healthcare systems, but it is not routinely reported in cancer registries. We developed an algorithm to identify patients who experienced recurrence or a second case of primary breast cancer (combined as a "second breast cancer event") using administrative data from the population of Ontario, Canada. A retrospective cohort study design was used including patients diagnosed with stage 0-III breast cancer in the Ontario Cancer Registry between 1 January 2009 and 31 December 2012 and alive six months post-diagnosis. We applied the algorithm to healthcare utilization data from six months post-diagnosis until death or 31 December 2013, whichever came first. We validated the algorithm's diagnostic accuracy against a manual patient record review (n = 2245 patients). The algorithm had a sensitivity of 85%, a specificity of 94%, a positive predictive value of 67%, a negative predictive value of 98%, an accuracy of 93%, a kappa value of 71%, and a prevalence-adjusted bias-adjusted kappa value of 85%. The second breast cancer event rate was 16.5% according to the algorithm and 13.0% according to manual review. Our algorithm's performance was comparable to previously published algorithms and is sufficient for healthcare system monitoring. Administrative data from a population can, therefore, be interpreted using new methods to identify new outcome measures. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this guideline is to determine the clinical utility of multigene profiling assays in individuals with early-stage invasive breast cancer. Methods: This guideline was developed by Ontario Health (Cancer Care Ontario)'s Program in Evidence-Based Care (PEBC) through a systematic review of relevant literature, patient- and caregiver-specific consultation and internal and external reviews. Recommendation 1: In patients with early-stage estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative breast cancer, clinicians should consider using multigene profiling assays (i.e., Oncotype DX, MammaPrint, Prosigna, EndoPredict, and the Breast Cancer Index) to help guide the use of systemic therapy. Recommendation 2: In patients with early-stage node-negative ER-positive/HER2-negative disease, clinicians may use a low-risk result from Oncotype DX, MammaPrint, Prosigna, EndoPredict/EPclin, or Breast Cancer Index assays to support a decision not to use adjuvant chemotherapy. Recommendation 3: In patients with node-negative ER-positive/HER2-negative disease, clinicians may use a high-risk result from Oncotype DX to support a decision to offer chemotherapy. A high Oncotype DX recurrence score is capable of predicting adjuvant chemotherapy benefit. Recommendation 4: In postmenopausal patients with ER-positive/HER2-negative tumours and one to three nodes involved (N1a disease), clinicians may withhold chemotherapy based on a low-risk Oncotype DX or MammaPrint score if the decision is supported by other clinical, pathological, or patient-related factors. Recommendation 5: The evidence to support the use of molecular profiling to select the duration of endocrine therapy is evolving. In patients with ER-positive disease, clinicians may consider using a Breast Cancer Index (H/I) high assay result to support a decision to extend adjuvant endocrine therapy if the decision is supported by other clinical, pathological, or patient-related factors. [ABSTRACT FROM AUTHOR]

Background BRCA1 and BRCA2 (BRCA) mutation carriers face a high lifetime risk of developing ovarian cancer. Oral contraceptives are protective in this population; however, the impact of other types of contraception (e.g. intrauterine devices, implants, injections) is unknown. We undertook a matched case-control study to evaluate the relationship between type of contraception and risk of ovarian cancer among women with BRCA mutations. Methods A total of 1733 matched pairs were included in this analysis. Women were matched according to year of birth, date of study entry, country of residence, BRCA mutation type and history of breast cancer. Detailed information on hormonal, reproductive and lifestyle exposures were collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with each contraceptive exposure. Results Ever use of any contraceptive was significantly associated with reduced risk of ovarian cancer (OR = 0.62; 95% CI 0.52–0.75; P < 0.0001), which was driven by significant inverse associations with oral contraceptives (OR = 0.66; 95% CI 0.54–0.79; P < 0.0001) and contraceptive implants (OR = 0.30; 95% CI 0.12–0.73; P = 0.008). We observed a similar effect with use of injections (OR = 0.37; 95% CI 0.10–1.38; P = 0.14), but this did not achieve significance. No significant associations were observed between patterns of intrauterine device use and risk of ovarian cancer. Conclusions These findings support a protective effect of oral contraceptives and implants on risk of ovarian cancer among women with BRCA mutations. The possible protective effect of injections requires further evaluation. • Whether other modes of contraception reduce the risk of ovarian cancer among BRCA mutation carriers has not been evaluated. • In this case-control study, use of contraceptive implants and oral contraceptives were inversely associated with risk. • There was a suggestive decreased risk with IUDs and injections; however, this was based on a small number of exposed cases. [ABSTRACT FROM AUTHOR]

Background: Rates of contralateral prophylactic mastectomy (CPM) are increasing among women with unilateral breast cancer despite low rates of contralateral recurrence and lack of survival benefit. We aimed to investigate the decisional needs and supports required to ensure adequate and quality decision-making by patients with breast cancer facing the decision regarding CPM.Methods: In this qualitative study, we used semistructured interviews developed with the use of the Ottawa Decision Support Framework to investigate the decisional needs and supports of women (aged > 18 yr) with nonhereditary breast cancer who had previously discussed CPM with their care provider. Patients were recruited from 2 academic cancer centres in Toronto, Ontario. Interviews were conducted between June 2016 and October 2017. We analyzed responses to the open-ended questions iteratively and inductively to establish major themes within the results.Results: Ten patients were recruited. Eight patients reported having initiated the discussion about CPM. Although most patients reported feeling supported, 6 mentioned some degree of decisional conflict. Cancer risk reduction was the most commonly reported perceived benefit of CPM (9 patients), followed by improved psychologic well-being (7). Most patients (8) did not mention the lack of survival benefit of CPM as a disadvantage of the procedure. Patients indicated that information resources (in 8 cases) and improved counselling from their health care team (in 7) would assist in decision-making.Conclusion: Our findings illustrate the disconnect between true and perceived risks (i.e., surgical risk) and benefits (potential recurrence and survival benefit) of CPM, which is not being managed adequately despite support from the health care team. A decision aid may address unmet patient need by providing a reliable resource regarding the benefits and risks of this procedure, while helping patients understand their values and realign their expectations. [ABSTRACT FROM AUTHOR]

BRCA mutation carriers face a high lifetime risk of developing ovarian cancer. The strong inverse association between breastfeeding and the risk of ovarian cancer is established in the general population but is less well studied among women with a germline BRCA1 or BRCA2 mutation. Thus, we conducted a matched case-control analysis to evaluate the association between breastfeeding history and the risk of developing ovarian cancer. After matching for year of birth, country of residence, BRCA gene and personal history of breast cancer, a total of 1650 cases and 2702 controls were included in the analysis. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence intervals (CI) associated with various breastfeeding exposures. A history of ever-breastfeeding was associated with a 23% reduction in risk (OR = 0.77; 95%CI 0.66–0.90; P = 0.001). The protective effect increased with breastfeeding from one month to seven months after which the association was relatively stable. Compared to women who never breastfed, breastfeeding for seven or more months was associated with a 32% reduction in risk (OR = 0.68; 95%CI 0.57–0.81; P < 0.0001) and did not vary by BRCA gene or age at diagnosis. The combination of breastfeeding and oral contraceptive use was strongly protective (0.47; 95%CI 0.37–0.58; P < 0.0001). These findings support a protective effect of breastfeeding for at least seven months among women with a BRCA1 or BRCA2 mutation, that is independent of oral contraceptive use. • Whether a history of breastfeeding is associated with the risk of ovarian cancer among BRCA mutation carriers is not known. • In this matched analysis, ever-breastfeeding was associated with a significant 23% reduction in risk of ovarian cancer. • We observed an additive effect of both oral contraceptive use and breastfeeding which was strongly protective. • Delineating the underlying mechanism(s) conferring the protective effect of breastfeeding is necessary. [ABSTRACT FROM AUTHOR]

Primary care providers will increasingly be tasked with managing most secondary findings from genomic sequencing, but literature exploring their capacity to manage findings beyond conventional genetic testing is limited. This study aimed t o explore primary care providers' challenges and potential solutions for managing secondary findings. Providers were recruited in two groups. Group 1 providers had a patient in their practice who received secondary findings and all potential group 1 providers were invited to participate. Group 2 providers were provided with the secondary findings of a hypothetical patient and were purposefully sampled for maximal variation in sex, practice setting, and geographic location. Providers were interviewed about their challenges and solutions managing secondary findings from a patient in their practice or a hypothetical patient. Using interpretive description methodology, transcripts were analysed thematically complemented by constant comparison. Out of the fifty-five providers invited, 15 family physicians participated across community and academic settings in Ontario, Canada (range 6–40 years in practice; 10/15 female). Providers described a responsibility to manage secondary findings, but limited capacity for this, describing practice, knowledge, and technical challenges. Providers expressed concern that compared to other incidental findings, secondary genomic findings might be reported directly to patients and result in longer-term anxiety. Potential solutions were a structured letter with categorized results and summary tables highlighting key secondary findings with follow-up recommendations and resources, as well as electronic medical records (EMRs) that store and integrate genomic information for prescribing or referrals. These solutions were deemed essential to address knowledge and technical challenges faced by primary care physicians and ultimately promote clinical utility of secondary findings. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to examine the impact of the level of HER2 overexpression on pathologic and clinical outcomes in HER2-positive breast cancer (BC) patients treated with neoadjuvant therapy (NAT)., Methods: Women with Stage II or III HER2-positive BC who received anthracycline-taxane-trastuzumab NAT regimens followed by curative-intent surgery were included. Patients were classified according to tumor HER2 expression into HER2-high (immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) HER2/CEP17 ratio ≥5 or HER2 copy number ≥10) and HER2-intermediate (IHC 2+ with HER2/CEP17 ratio ≥2 to <5 or copy number ≥4 to <10). Univariate and multivariate logistic regression analyses were performed using HER2 expression as a categorical variable. The primary outcome was pathological complete response (pCR). Estimated 3-year disease-free survival (DFS) and Overall Survival (OS) were secondary outcomes., Results: Among 161 patients with HER2-positive BC, 139 (86%) and 22 (14%) were classified as HER2-high and HER2-intermediate, respectively; 105 (65.2%) had hormone receptor (HR)-positive tumors; 72 (45%) achieved a pCR. In the overall population, pCR rates of 18% and 49% were achieved in HER2-intermediate and HER2-high cases, respectively (odds ratio [OR] = 0.23 95% CI 0.07-0.72; P = .007). No pCRs were observed among HR-positive, HER2-intermediate cases. Estimated 3-year DFS was 97.1% versus 89.3% for patients achieving a pCR versus those with residual disease, respectively (P = .0011)., Conclusion: We found that patients with HER2-high disease were more likely to achieve pCR after NAT compared to patients with HER2-intermediate BC, a subgroup of patients that may benefit from more personalized NAT strategies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Neoadjuvant chemotherapy (NAC) for triple-negative (TN) and Her2-positive (HER2) breast cancers is supported by international guidelines as it can decrease extent of surgery, provide prognostic information, and allow response-driven adjuvant therapies. Our goal was to describe practice patterns for patients with TN and HER2-positive breast cancer and identify the factors associated with the receipt of NAC versus surgery as initial treatment., Methods: A retrospective population-based cohort study of adult women diagnosed with stage I-III TN or HER2-positive breast cancer (2012-2020) in Ontario was completed using linked administrative datasets. The primary outcome was NAC as first treatment. The association between NAC and patient, tumor, and practice-related factors was examined using multivariable logistic regression models., Results: Of 14,653 patients included, 23.9% (n = 3500) underwent NAC as first treatment. Patients who underwent NAC were more likely to be younger and have larger tumors, node-positive disease, and stage 3 disease. Of patients who underwent surgery first, 8.8% were seen by a medical oncologist prior to surgery. On multivariable analysis, increasing tumor size (T2 vs T1/T0: 2.75 (2.31-3.28)) and node-positive (N1 vs N0: OR 3.54 (2.92-4.30)) disease were both associated increased odds of receiving NAC., Conclusion: A considerable proportion of patients with TN and HER2-positive breast cancer do not receive NAC as first treatment. Of those, most were not assessed by both a surgeon and medical oncologist prior to initiating therapy. This points toward potential gaps in multidisciplinary assessment and disparities in receipt of guideline-concordant care., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)