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1.
Nat Cancer ; 3(10): 1181-1191, 2022 10.
Article in English | MEDLINE | ID: mdl-36253484

ABSTRACT

Talazoparib, a PARP inhibitor, is active in germline BRCA1 and BRCA2 (gBRCA1/2)-mutant advanced breast cancer, but its activity beyond gBRCA1/2 is poorly understood. We conducted Talazoparib Beyond BRCA ( NCT02401347 ), an open-label phase II trial, to evaluate talazoparib in patients with pretreated advanced HER2-negative breast cancer (n = 13) or other solid tumors (n = 7) with mutations in homologous recombination (HR) pathway genes other than BRCA1 and BRCA2. In patients with breast cancer, four patients had a Response Evaluation Criteria in Solid Tumors (RECIST) partial response (overall response rate, 31%), and three additional patients had stable disease of ≥6 months (clinical benefit rate, 54%). All patients with germline mutations in PALB2 (gPALB2; encoding partner and localizer of BRCA2) had treatment-associated tumor regression. Tumor or plasma circulating tumor DNA (ctDNA) HR deficiency (HRD) scores were correlated with treatment outcomes and were increased in all gPALB2 tumors. In addition, a gPALB2-associated mutational signature was associated with tumor response. Thus, talazoparib has been demonstrated to have efficacy in patients with advanced breast cancer who have gPALB2 mutations, showing activity in the context of HR pathway gene mutations beyond gBRCA1/2.


Subject(s)
Breast Neoplasms , Circulating Tumor DNA , Humans , Female , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , Homologous Recombination , Breast Neoplasms/drug therapy , Mutation , BRCA1 Protein/genetics , BRCA2 Protein/genetics
2.
CMAJ Open ; 5(1): E14-E18, 2017.
Article in English | MEDLINE | ID: mdl-28401113

ABSTRACT

BACKGROUND: Health research provides a means to define health status and to identify ways to improve health. Our objective was to define the proportion of grants and funding from the Government of Canada's health research investment agency, the Canadian Institutes of Health Research (CIHR), that was awarded for prison health research, and to describe the characteristics of funded grants. METHODS: In this descriptive study, we defined prison health research as research on the health and health care of people in prisons and at the time of their release. We searched the CIHR Funding Decisions Database by subject and by investigator name for funded grants for prison health research in Canada in all competitions between 2010 and 2014. We calculated the proportion of grants and funding awarded for prison health research, and described the characteristics of funded grants. RESULTS: During the 5-year study period, 21 grants were awarded that included a focus on prison health research, for a total of $2 289 948. Six of these grants were operating grants and 6 supported graduate or fellowship training. In total, 0.13% of all grants and 0.05% of all funding was for prison health research. INTERPRETATION: A relatively small proportion of CIHR grants and funding were awarded for prison health research between 2010 and 2014. If prison health is a priority for Canada, strategic initiatives that include funding opportunities could be developed to support prison health research in Canada.

4.
J Obstet Gynaecol Can ; 38(9): 820-826, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27670707

ABSTRACT

OBJECTIVE: Studies from the United States have shown that women in correctional facilities have higher rates of unintended pregnancy and unmet need for contraception compared with the general population, and that the provision of family planning services in correctional facilities may improve access to contraception. No study has examined these issues in women in correctional facilities in Canada. We aimed to describe the rates of unintended pregnancy and contraceptive use for incarcerated women in Ontario. METHODS: Women in a provincial correctional facility in Ontario completed a written survey in 2014. We calculated the prevalence of prior unintended pregnancy, prior therapeutic abortion, and contraception use. We calculated the unmet need for contraception, defined as the proportion of women who were not using reliable contraception among women who were sexually active and were not trying to conceive. RESULTS: Of 85 participants, 82% had been pregnant, and of these women, 77% had experienced an unintended pregnancy and 57% reported having undergone a therapeutic abortion. Regarding the most recent pregnancy, 72% of women scored their pregnancy intention as unplanned or ambivalent. Of women who were at risk for unintended pregnancy prior to incarceration, 80% were not using a reliable form of contraception. CONCLUSION: Incarcerated women in Ontario have higher rates of unintended pregnancy and unmet need for contraception than does the general population. The provision of family planning services during and after incarceration may improve the health of individuals and reduce costs for society overall.

5.
BMC Res Notes ; 9: 131, 2016 Feb 29.
Article in English | MEDLINE | ID: mdl-26923923

ABSTRACT

BACKGROUND: Little is known about access to primary care either prior to or following incarceration in Canada. International data demonstrate that the health of people in prisons and jails is poor, and access to primary care in the community may be inadequate for incarcerated persons. We aimed to describe the primary care experience of adults in custody in a provincial correctional facility in Ontario in the 12 months prior to admission. METHODS: We conducted a written survey, and invited all persons in the institution to participate, excluding those in segregation. RESULTS: One hundred and twenty-five persons participated, 16.8% of whom were women. The median age was 33. In the 12 months prior to admission to custody, 32.2% (95% CI 23.5-40.8%) of respondents did not have a family doctor or other primary care provider and 48.2% (95% CI 38.8-57.6%) had unmet health needs. Participants reported a mean of 2.1 (SD = 2.8) emergency department visits in the 12 months prior to admission. CONCLUSIONS: Study participants report a lack of access to primary care, a high mean number of emergency department visits, and high unmet health care needs in the 12 months prior to incarceration. Time in custody may present an opportunity for connecting this population with primary care and improving health.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Health Services Accessibility/ethics , Office Visits/statistics & numerical data , Primary Health Care/statistics & numerical data , Prisoners , Adult , Chronic Disease , Female , Humans , Male , Middle Aged , Ontario , Primary Health Care/ethics , Retrospective Studies
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