Vasily Giannakeas

Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ

IMPORTANCE Women with ductal carcinoma in situ (DCIS), or stage 0 breast cancer, often experience a second primary breast cancer (DCIS or invasive), and some ultimately die of breast cancer. OBJECTIVE To estimate the 10- and 20-year mortality from breast cancer following a diagnosis of DCIS and to establish whether the mortality rate is influenced by age at diagnosis, ethnicity, and initial treatment received. DESIGN, SETTING, AND PARTICIPANTS Observational study of women who received a diagnosis of DCIS from 1988 to 2011 in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Age at diagnosis, race/ethnicity, pathologic features, date of second primary breast cancer, cause of death, and survival were abstracted for 108,196 women. Their risk of dying of breast cancer was compared with that of women in the general population. Cox proportional hazards analysis was performed to estimate the hazard ratio (HR) for death from DCIS by age at diagnosis, clinical features, ethnicity, and treatment. MAIN OUTCOMES AND MEASURES Ten- and 20-year breast cancer-specific mortality. RESULTS Among the 108 196 women with DCIS, the mean (range) age at diagnosis of DCIS was 53.8 (15-69) years and the mean (range) duration of follow-up was 7.5 (0-23.9) years. At 20 years, the breast cancer-specific mortality was 3.3% (95% CI, 3.0%-3.6%) overall and was higher for women who received a diagnosis before age 35 years compared with older women (7.8% vs 3.2%; HR, 2.58 [95% CI, 1.85-3.60]; P < .001) and for blacks compared with non-Hispanic whites (7.0% vs 3.0%; HR, 2.55 [95% CI, 2.17-3.01]; P < .001). The risk of dying of breast cancer increased after experience of an ipsilateral invasive breast cancer (HR, 18.1 [95% CI, 14.0-23.6]; P < .001). A total of 517 patients died of breast cancer following a DCIS diagnosis (mean follow-up, 7.5 [range, 0-23.9] years) without experiencing an in-breast invasive cancer prior to death. Among patients who received lumpectomy, radiotherapy was associated with a reduction in the risk of ipsilateral invasive recurrence at 10 years (2.5% vs 4.9%; adjusted HR, 0.47 [95% CI, 0.42-0.53]; P < .001) but not of breast cancer-specific mortality at 10 years (0.8% vs 0.9%; HR, 0.86 [95% CI, 0.67-1.10]; P = .22). CONCLUSIONS AND RELEVANCE Important risk factors for death from breast cancer following a DCIS diagnosis include age at diagnosis and black ethnicity. The risk of death increases after a diagnosis of an ipsilateral second primary invasive breast cancer, but prevention of these recurrences by radiotherapy does not diminish breast cancer mortality at 10 years.

Why have ovarian cancer mortality rates declined? Part III. Prospects for the future

Over the last 40 years, the age-adjusted ovarian cancer mortality rate in the USA declined by 23%. The decline in mortality paralleled a decline in incidence, which was largely due to changes in reproductive risk factors. There was no reduction in ovarian cancer case-fatality at 12 years, indicating that improvements in early detection or in treatment did not contribute to the decline in mortality. Here, we discuss potential strategies to further reduce ovarian cancer mortality through prevention, early detection and treatment. The first approach is to increase genetic testing, in order to identify women who are at a high risk of developing ovarian cancer and offer them preventive bilateral salpingo-oophorectomy. At present, up to 17% of ovarian cancers are potentially preventable through population-based genetic testing of known ovarian cancer susceptibility genes. The second approach is to increase the proportion of ovarian cancer patients who achieve a status of no residual disease through primary debulking surgery and subsequently receive adjuvant intraperitoneal chemotherapy. We believe that through a combination of screening to better identify low-volume advanced stage ovarian cancer, aggressive surgery to leave no residual disease and adjuvant intraperitoneal chemotherapy, the cure rate of ovarian cancer might be improved significantly.

Predictors and Outcomes of Dysphagia Screening After Acute Ischemic Stroke

Background and Purpose— Guidelines advocate screening all acute stroke patients for dysphagia. However, limited data are available regarding how many and which patients are screened and how failing a swallowing screen affects patient outcomes. We sought to evaluate predictors of receiving dysphagia screening after acute ischemic stroke and outcomes after failing a screening test. Methods— We used the Ontario Stroke Registry from April 1, 2010, to March 31, 2013, to identify patients hospitalized with acute ischemic stroke and determine predictors of documented dysphagia screening and outcomes after failing the screening test, including pneumonia, disability, and death. Results— Among 7171 patients, 6677 patients were eligible to receive dysphagia screening within 72 hours, yet 1280 (19.2%) patients did not undergo documented screening. Patients with mild strokes were significantly less likely than those with more severe strokes to have documented screening (adjusted odds ratio, 0.51; 95% confidence interval [CI], 0.41–0.64). Failing dysphagia screening was associated with poor outcomes, including pneumonia (adjusted odds ratio, 4.71; 95% CI, 3.43–6.47), severe disability (adjusted odds ratio, 5.19; 95% CI, 4.48–6.02), discharge to long-term care (adjusted odds ratio, 2.79; 95% CI, 2.11–3.79), and 1-year mortality (adjusted hazard ratio, 2.42; 95% CI, 2.09–2.80). Associations were maintained in patients with mild strokes. Conclusions— One in 5 patients with acute ischemic stroke did not have documented dysphagia screening, and patients with mild strokes were substantially less likely to have documented screening. Failing dysphagia screening was associated with poor outcomes, including in patients with mild strokes, highlighting the importance of dysphagia screening for all patients with acute ischemic stroke.

A model for estimating ovarian cancer risk: Application for preventive oophorectomy

OBJECTIVE It is important to identify women in the population who have a high risk of ovarian cancer and who might benefit from prophylactic bilateral salpingo-oophorectomy. The probability that a woman will develop ovarian cancer depends on her current age, her reproductive history and her genetic status. METHODS We simulated the distribution of ovarian cancer risk for the 2011 Ontario female population. We generated (at random) individual risks of ovarian cancer to age 80 for 6,301,340 women, based on the published risk factors, mutation frequencies and population age-specific incidence rates (SEER database). Risk factors included parity, breastfeeding, oral contraceptives, tubal ligation and family history. Genetic factors included 11 single nucleotide polymorphisms (SNPs) and BRCA1/2 mutations. RESULTS Of the 6,301,340 women simulated as the general population of Ontario, the (complete) model predicts that 65,805 women (1.0%) will develop ovarian cancer by age 80. There were 46,069 women (0.7%) with a risk of ovarian cancer above 5%. BRCA1/2 mutation carriers accounted for 67.4% of the women at greater than 5% risk (31,028 women). Among ovarian cancer patients at greater than 5% risk, a BRCA1/2 mutation was present in 89.2%. In contrast, SNPs contribute to a very small proportion of the ovarian cancer patients who were at greater than 5% risk. CONCLUSIONS Approximately 12.9% of all ovarian cancers in Ontario occur in the 0.7% of women in the general population who have a lifetime ovarian cancer risk in excess of 5%, the majority of whom carry a mutation in BRCA1 or BRCA2.

Association of Radiotherapy With Survival in Women Treated for Ductal Carcinoma In Situ With Lumpectomy or Mastectomy

Key Points Question Is adjuvant radiation associated with a reduction in breast cancer mortality in patients treated for ductal carcinoma in situ? Findings Using a matched approach in a large cohort of patients treated for ductal carcinoma in situ, treatment with lumpectomy and radiotherapy was associated with a significantly reduced risk of breast cancer–specific mortality compared with treatment with lumpectomy alone (hazard ratio, 0.77; 95% CI, 0.67-0.88) or mastectomy alone (hazard ratio, 0.75; 95% CI, 0.65-0.87). Meaning Adjuvant radiation is associated with a small but significant breast cancer survival benefit in patients with ductal carcinoma in situ that cannot be accounted for by enhancing local control.

Comparison of prescribing practices for older adults treated by female versus male physicians: A retrospective cohort study

Importance Subtle but important differences have been described in the way that male and female physicians care for their patients, with some evidence suggesting women are more likely to adhere to best practice recommendations. Objective To determine if male and female physicians differ in their prescribing practices as measured by the initiation of lower-than-recommended dose cholinesterase inhibitor (ChEI) drug therapy for dementia management. Design, setting, and participants All community-dwelling Ontario residents aged 66 years and older with dementia and newly dispensed an oral ChEI drug (donepezil, galantamine, or rivastigmine) between April 1, 2010 and June 30, 2016 were included. Main outcome and measures The association between physician sex and the initiation of a lower than recommended-dose ChEI was examined using generalized linear mixed regression models, adjusting for patient and physician characteristics. Data were stratified by specialty. Secondary analyses explored the association between physician sex and cardiac screening as well as shorter duration of the initial prescription. Results The analysis included 3,443 female and 5,811 male physicians and the majority (83%) were family physicians, Female physicians were more likely to initiate ChEI therapy at a lower-than-recommended dose (Adjusted odds ratio = 1.43,95% confidence interval = 1.17 to 1.74). Compared to their male counterparts, female physicians were also more likely to follow other conservative prescribing practices including cardiac screening (55.1% vs. 49.2%, P-value<0.001) around the time of ChEI initiation, and dispensing a shorter duration of initial prescription (41.8% vs 35.5% P-value<0.001). Conclusions There is a statistically significant and important difference in ChEI prescribing patterns between female and male physicians, suggesting that female physicians may be more careful and conservative in their approaches. This will inform future research to determine if patients receiving lower-than-recommended initial doses also have better outcomes.

Denosumab and breast cancer risk in postmenopausal women: a population-based cohort study

BackgroundDenosumab inhibits the receptor activator of nuclear factor κB (RANK) pathway and is used to treat osteoporosis. Emerging evidence suggests RANK-blockade may play a role in mammary tumourigenesis. Thus, we undertook a population-based study of denosumab use and breast cancer risk in a large cohort of postmenopausal women.MethodsWe included women 67+ years with prior bisphosphonate use who filled a first prescription for denosumab. They were matched on age, date, cumulative prior use of and time since last use of a bisphosphonate to women with no history of denosumab. Cox proportional hazards was used to estimate the hazard ratio (HR) of breast cancer with denosumab use.ResultsA total of 100,368 women were included in the analysis with 1271 incident breast cancer events. Denosumab use was associated with a 13% decreased breast cancer risk (HR = 0.87; 95% CI 0.76–1.00). There was no relationship between increasing number of denosumab doses and breast cancer risk (P-trend = 0.15).ConclusionThese findings suggest a potential protective effect of ever denosumab use on breast cancer risk in a cohort of older women previously treated with bisphosphonates.