Breast Cancer Polygenic-Risk Score Influence on Risk-Reducing Endocrine Therapy Use: Genetic Risk Estimate (GENRE) Trial 1-Year and 2-Year Follow-Up.

Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors. PREVENTION RELEVANCE: Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.

Bone mineral density and risk of postmenopausal breast cancer.

To determine if higher bone mineral density (BMD) is a risk factor for breast cancer in women age 50 years and older. 37,860 women ≥ 50-year old with no previous breast cancer diagnosis had baseline BMD assessment between January 1999 and December 2007. Cox proportional hazards models were created for time to a new breast cancer as a function of lumbar spine or femoral neck BMD quartile (1st = lowest as reference) with adjustment for relevant covariates. A secondary analysis was performed to look for an association with estrogen receptor-positive (ER-positive) breast cancers. 794 invasive and in situ breast cancers (484 ER-positive) occurred with a median follow up of 5.4 years. Increased breast cancer risk was seen for the 3rd and 4th quartiles of lumbar spine BMD with hazard ratios (HRs) of 1.26 (95% CI, 1.01-1.58) and 1.45 (95% CI, 1.16-1.81), respectively and for the 3rd quartile of femoral neck BMD with a HR of 1.33 (95% CI, 1.07-1.64). A test for linear trend showed that lumbar spine BMD (P < 0.001) and femoral neck BMD (P = 0.04) were associated with increased risk. Higher lumbar spine BMD was also associated with increased risk of ER-positive breast cancer with HR of 1.45 (95% CI, 1.08-1.94), and 1.68 (95% CI, 1.24-2.27) for women in the 2nd and 4th quartiles, respectively. A test for linear trend showed lumbar spine BMD was associated with increasing risk of ER-positive breast cancer (P = 0.003). Increased ER-positive breast cancer risk was seen for the 3rd quartile of femoral neck BMD with a HR of 1.43 (95% CI, 1.08-1.89). Higher lumbar spine and femoral neck BMD are associated with higher risk of breast cancer in women ≥50-year old. Lumbar spine and femoral neck BMD are associated with increased risk of ER-positive breast cancer.

Prognostic factors depicting disease-specific survival in parotid-gland tumors.

PURPOSE: To identify significant prognostic factors that can be used in clinical decision-making with regard to parotid cancer, which is characterized by a complex and diverse group of tumors with variable outcomes. METHODS AND MATERIALS: A historical cohort of 184 patients with parotid-gland malignancy, who had been registered in the Province of Manitoba from 1970 to 2003, was examined. Survival analysis was performed using Kaplan-Meier curves and a log-rank test for comparing subgroups. The independent effect of factors that predicted survival at the bivariate level was determined using a Cox proportional hazard model. RESULTS: The mean age at presentation was 62 years. The mean follow-up was 64 months. Absolute and disease-specific survival at 5 years was 41.70% and 57.94%, respectively. Survival for Stages I-IV at 5 years was 85.35%, 76.9%, 56.1%, and 8.4%, respectively (p < 0.0001). Factors with an independent effect on survival (p < 0.05) included age, tumor size, local invasion (Stages T4 vs. T1), and distant metastasis at presentation, tumor differentiation, and treatment. Adjuvant radiotherapy vs. surgery alone reduced the risk of death from disease at 5 years by 50% (hazard ratio [HR], 0.5; 95% confidence interval, 0.228-0.995; p = 0.0486). CONCLUSIONS: Despite the variety of malignant parotid tumors, easily identifiable prognostic indicators such as advanced age, tumor size, local invasion, and tumor differentiation have a significant impact on outcome. Patients with adverse prognostic factors benefit from adjuvant radiotherapy. The threshold for the use of adjuvant radiotherapy in managing parotid malignancy should be low.

Efficacy of complete decongestive therapy and manual lymphatic drainage on treatment-related lymphedema in breast cancer.

OBJECTIVE: To evaluate the results of combined decongestive therapy and manual lymphatic drainage in patients with breast cancer-related lymphedema. METHODS AND MATERIALS: The data from 250 patients were reviewed. The pre- and posttreatment volumetric measurements were compared, and the correlation with age, body mass index, and type of surgery, chemotherapy, and radiotherapy was determined. The Spearman correlation coefficients and Wilcoxon two-sample test were used for statistical analysis. RESULTS: Of the 250 patients, 138 were included in the final analysis. The mean age at presentation was 54.3 years. Patients were stratified on the basis of the treatment modality used for breast cancer management. Lymphedema was managed with combined decongestive therapy in 55%, manual lymphatic drainage alone in 32%, and the home program in 13%. The mean pretreatment volume of the affected and normal arms was 2929 and 2531 mL. At the end of 1 year, the posttreatment volume of the affected arm was 2741 mL. The absolute volume of the affected arm was reduced by a mean of 188 mL (p < 0.0001). The type of surgery (p = 0.0142), age (p = 0.0354), and body mass index (p < 0.0001) were related to the severity of lymphedema. CONCLUSION: Combined decongestive therapy and manual lymphatic drainage with exercises were associated with a significant reduction in the lymphedema volume.

Radiation Therapy Versus No Radiation Therapy to the Neo-breast Following Skin-Sparing Mastectomy and Immediate Autologous Free Flap Reconstruction for Breast Cancer: Patient-Reported and Surgical Outcomes at 1 Year-A Mastectomy Reconstruction Outcomes Consortium (MROC) Substudy.

PURPOSE: To determine whether adjuvant radiation therapy (RT) is associated with adverse patient-reported outcomes and surgical complications 1 year after skin-sparing mastectomy and immediate autologous free flap reconstruction for breast cancer. METHODS AND MATERIALS: We compared 24 domains of patient-reported outcome measures 1 year after autologous reconstruction between patients who received adjuvant RT and those who did not. A total of 125 patients who underwent surgery between 2012 and 2015 at our institution were included from the Mastectomy Reconstruction Outcomes Consortium study database. Adjusted multivariate models were created incorporating RT technical data, age, cancer stage, estrogen receptor, chemotherapy, breast size, body mass index, and income to determine whether RT was associated with outcomes. RESULTS: At 1 year after surgery, European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer-Specific Quality of Life Questionnaire breast symptoms were significantly greater in 64 patients who received RT (8-point difference on 100-point ordinal scale, P<.0001) versus 61 who did not receive RT in univariate and multivariate models. EORTC arm symptoms (20-point difference on 100-point ordinal scale, P=.0200) differed on univariate analysis but not on multivariate analysis. All other outcomes-including Numerical Pain Rating Scale, BREAST-Q (Post-operative Reconstruction Module), Patient-Report Outcomes Measurement Information System Profile 29, McGill Pain Questionnaire-Short Form (MPQ-SF) score, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-were not statistically different between groups. Surgical complications were uncommon and did not differ by treatment. CONCLUSIONS: RT to the neo-breast compared with no RT following immediate autologous free flap reconstruction for breast cancer is well tolerated at 1 year following surgery despite patients undergoing RT also having a higher cancer stage and more intensive surgical and systemic treatment. Neo-breast symptoms are more common in patients receiving RT by the EORTC Breast Cancer-Specific Quality of Life Questionnaire but not by the BREAST-Q. Patient-reported results at 1 year after surgery suggest RT following immediate autologous free flap breast reconstruction is well tolerated.

Prospective functional outcomes in sequential population based cohorts of stage III/ IV oropharyngeal carcinoma patients treated with 3D conformal vs. intensity modulated radiotherapy.

BACKGROUND AND PURPOSE: To compare early (3 and 6 month) and later (12 and 24 month) functional outcomes of stage III and IV (M0) oropharyngeal squamous cancer patients treated in sequential cohorts with 3D conformal (3DCRT) or intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: 200 patients in sequential population based cohorts of 83 and 117 patients treated at a single institution with 3DCRT and then IMRT respectively were prospectively assessed at pre-treatment and 3, 6, 12 and 24 months post treatment. A standard functional outcomes protocol including performance status (KPS, ECOG), 3 Performance Status scales for Head and Neck (PSS-HN), the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), Voice Handicap Index-10 (VHI-10) and self-rated xerostomia were applied. RESULTS: Mean age at diagnosis was 59 years. The primary site was base of tongue in 77 and tonsil or soft palate in 123 patients. Median follow up was 2.5 years for the second cohort. Concomitant therapy was used in 159 (79.5%). Overall survival at 3 years was 75.6% and 71.5% for IMRT and 3DCRT cohorts respectively (not significant). A multiple imputation technique was used to estimate missing values in order to avoid a healthy patient bias. KPS and ECOG reached nadirs at 3 to 6 months but approached baseline values at 12 to 24 months and did not differ by treatment. The 3 PSS-HN scales, Eating in Public (p < 0.001), Understandability of Speech (p = 0.009) and Oral Diet Texture (p = 0.002) and all showed significantly better outcomes in favor of IMRT. The RBHOMS showed a difference in favor of IMRT which appeared during 3 to 6 months (p < 0.001). The VHI-10 also showed a difference in favor of IMRT (p = 0.015). Self-rated xerostomia did not differ at 3 and 6 months but was significantly better in favor of IMRT after 12 months p = 0.005 CONCLUSIONS: A prospectively administered functional outcomes protocol showed meaningful differences in favor of IMRT over 3DCRT early (3-6 months) and later (12-24 months) in the treatment of oropharyngeal carcinoma with equivalent survival. These data support the adoption of IMRT as the standard radiation treatment method for patients with stage III and IV (M0) oropharyngeal squamous carcinoma. KPS and ECOG may not be sensitive to oropharyngeal cancer patients' functional outcomes by treatment.

Quality of life in MAP.3 (Mammary Prevention 3): a randomized, placebo-controlled trial evaluating exemestane for prevention of breast cancer.

PURPOSE: Exemestane, a steroidal aromatase inhibitor, reduced invasive breast cancer incidence by 65% among 4,560 postmenopausal women randomly assigned to exemestane (25 mg per day) compared with placebo in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MAP.3 (Mammary Prevention 3) trial, but effects on quality of life (QOL) were not fully described. PATIENTS AND METHODS: Menopause-specific and health-related QOL were assessed by using the four Menopause-Specific Quality of Life Questionnaire (MENQOL) domains and the eight Medical Outcomes Study Short Form Health Survey (SF-36) scales at baseline, 6 months, and yearly thereafter. MENQOL questionnaire completion was high (88% to 98%) in both groups at each follow-up visit. Change scores for each MENQOL and SF-36 scale, calculated at each assessment time relative to baseline, were compared by using the Wilcoxon rank-sum test. Clinically important worsened QOL was defined as a MENQOL change score increase of more than 0.5 (of 8) points and an SF-36 change score decrease of more than 5 (of 100) points from baseline. RESULTS: Exemestane had small negative effects on women's self-reported vasomotor symptoms, sexual symptoms, and pain, which occurred mainly in the first 6 months to 2 years after random assignment. However, these changes represented only a small excess number of women being given exemestane with clinically important worsening of QOL at one time or another; specifically, 8% more in the vasomotor domain and 4% more each in the sexual domain and for pain. No other between-group differences were observed. Overall, slightly more women in the exemestane arm (32%) than in the placebo arm (28%) discontinued assigned treatment. CONCLUSION: Exemestane given for prevention has limited negative impact on menopause-specific and health-related QOL in healthy postmenopausal women at risk for breast cancer.

Utilization of preoperative radiation therapy in the management of rectal cancer: A population-based analysis.

PURPOSE: Preoperative radiation therapy (RT) improves local control in resectable rectal cancer compared with postoperative RT or surgery alone. Although clinical practice guidelines exist, adherence to recommendations for preoperative RT is unclear. This population-based study examines preoperative RT utilization rates for rectal cancer patients in a Canadian province and investigates factors influencing its usage. METHODS AND MATERIALS: Between 2004 and 2009, all stage II and III rectal cancer patients treated with definitive surgery were identified using the Manitoba Cancer Registry. Patients not receiving resection of the primary tumor, as determined by administrative procedure codes, were excluded. Factors potentially influencing preoperative RT utilization, including age, gender, stage, year of diagnosis, and geographic distance from RT facility, were analyzed using logistic regression analyses. Overall survival outcomes were also examined. RESULTS: The registry identified 776 patients meeting the study inclusion criteria. Preoperative RT utilization increased from 3% in 2004 to 41% in 2009. Postoperative RT utilization decreased from 48% to 17% during the same period. Rates of surgery alone remained stable at 40%-50%. Factors influencing preoperative RT utilization were younger age (P < .0001), stage III disease (P = .02), and later year of diagnosis (P < .0001). Elderly patients age 70 years and over were predominantly treated with surgery alone. Actuarial 5-year overall survival for patients receiving preoperative RT postoperative RT, and surgery alone were 80%, 73%, and 58%, respectively. CONCLUSIONS: Steadily increasing utilization of preoperative compared with postoperative RT is evident; however, rates of surgery alone remained unchanged. Strategies to improve preoperative RT utilization, particularly among elderly patients, are needed.

Tamoxifen use and osteoporotic fracture risk: a population-based analysis.

PURPOSE: Although tamoxifen has been shown to increase bone mineral density in clinical trials, it is less clear whether this significantly affects fracture rates. Even fewer data are available on skeletal outcomes when tamoxifen is used outside of the context of a clinical trial. A population-based case-control study was undertaken to determine whether tamoxifen use is associated with osteoporotic fractures in routine clinical practice. PATIENTS AND METHODS: Population-based administrative data for the Province of Manitoba, Canada, were examined for tamoxifen use and nontraumatic fracture codes in women 50 years of age or older. Women with osteoporotic fractures (vertebral, wrist or hip; n = 11,096) from 1996 to 2004 were each compared with three controls without fracture, matched for age, ethnicity, and comorbidity (n = 33,209). Tamoxifen use was classified as never, past use, or current use. RESULTS: Lower osteoporotic fracture rates were associated with current tamoxifen use (univariate odds ratio [OR] = 0.68; 95% CI, 0.55 to 0.84). After controlling for demographic and medical diagnoses known to affect fracture risk, current use was associated with a significantly reduced overall osteoporotic fracture risk (adjusted OR = 0.68; 95% CI, 0.55 to 0.88) and of hip fractures (adjusted OR = 0.47; 95% CI, 0.28 to 0.77). Neither recent nor remote past tamoxifen use was associated with reduced osteoporotic fracture risk. Breast cancer was not independently associated with osteoporotic fractures (adjusted OR = 0.95; 95% CI, 0.81 to 1.12). CONCLUSION: In a population-based case-control study, current tamoxifen use was associated with a substantial reduction in osteoporotic fractures.