Referral, Genetic Counselling, and BRCA Testing in the Manitoba High-Grade Serous Ovarian Cancer Population, 2004–2019

Round 1

Reviewer 1 Report

    Generally speaking, this article “Referral, genetic counselling, and BRCA testing in the Manitoba high grade serous ovarian cancer population, 2004-2019” is written clear and concise. The paper is a long time range public health statistics review paper.

    However, in the current article, only the relationship between BRCA testing and the ovarian cancer population is mainly. and divided into three time intervals (2004-2013, 2014-2016, 2017-2019). The rate of genetic referrals changed over the entire frames (20%, 56.7%, 36.6%). Based on the theories of molecular biology of cancer, seems a little weak of evidence.

    Is it possible to combine this paper with the paper on cellular molecular biology, information transmission pathways.  Such as “RNase1 will become a new biomarker in breast cancer research diagnosis” (NATURE COMMUNICATIONS | (2021) 12:2788 | https://doi.org/10.1038/s41467-021-23075-2 | www.nature.com/naturecommunications).  Although it seems a bit difficult to do this work, these two types of articles are usually carried out separately! That is, there is a paper on cellular biology signal transduction analysis, and then there is a basic theory to analyze the paper supporting clinical public health statistics. Consider and review together signal transduction pathway. Compare the two sides to find out the cause of the new Biomarker or the new ovarian cancer (high-grade serous ovarian cancers, HGSOC).

Author Response

Reviewer 1:

Generally speaking, this article “Referral, genetic counselling, and BRCA testing in the Manitoba high grade serous ovarian cancer population, 2004-2019” is written clear and concise. The paper is a long time range public health statistics review paper.
    However, in the current article, only the relationship between BRCA testing and the ovarian cancer population is mainly. and divided into three time intervals (2004-2013, 2014-2016, 2017-2019). The rate of genetic referrals changed over the entire frames (20%, 56.7%, 36.6%). Based on the theories of molecular biology of cancer, seems a little weak of evidence.
    Is it possible to combine this paper with the paper on cellular molecular biology, information transmission pathways.  Such as “RNase1 will become a new biomarker in breast cancer research diagnosis” (NATURE COMMUNICATIONS | (2021) 12:2788 | https://doi.org/10.1038/s41467-021-23075-2 | www.nature.com/naturecommunications).  Although it seems a bit difficult to do this work, these two types of articles are usually carried out separately! That is, there is a paper on cellular biology signal transduction analysis, and then there is a basic theory to analyze the paper supporting clinical public health statistics. Consider and review together signal transduction pathway. Compare the two sides to find out the cause of the new Biomarker or the new ovarian cancer (high-grade serous ovarian cancers, HGSOC).

Response:

Thank you for reviewing this manuscript. The primary objective of our study was to determine the rate of genetic referral, rate of testing for germline BRCA1 and BRCA2 mutations, and rate of BRCA positivity amongst women diagnosed with high-grade serous ovarian cancer. By using this population-based real-world data, we can understand better the care that women are receiving and identify current gaps that need to be addressed. As you mentioned above, the cohort was divided into three time periods. This was done to correlate with known practice changes, and is therefore reflected in the changing rate of genetic referrals. This study was a population based trial with no basic science component investigating molecular biology of cancer, other than the well-established risk of ovarian cancer imparted by BRCA mutations.  While it is not possible to combine this paper with a paper on cellular molecular biology, members of the MOCR study team are currently doing work in this area.

Reviewer 2 Report

The article does not seem particularly groundbreaking to me but may be interesting to review the rate of patients who are afferent to genetic testing in the 2004-2019 time frame and the influencing factors.

Perhaps an in-depth article on secondary goals ( which seem to me to be more interesting to explore) might be of more interest.

 I didn't understand the content and meaning of the "simple summary" as it is written

Author Response

Reviewer 2:

The article does not seem particularly groundbreaking to me but may be interesting to review the rate of patients who are afferent to genetic testing in the 2004-2019 time frame and the influencing factors.
Perhaps an in-depth article on secondary goals ( which seem to me to be more interesting to explore) might be of more interest.
 I didn't understand the content and meaning of the "simple summary" as it is written

Response:

Thank you for reviewing this manuscript and expressing your interest in secondary goals. We believe that papers such as ours contribute to the on-going identification of gaps in care that can be addressed and are therefore an important addition to the literature. We agree that examining predictors of referral and testing is an important area of research and our paper did correlated predictors with referral rates using the data that was available. Our statements regarding secondary factors are indicated in the abstract and in the results and summarized by these sections:

“Factors found to increase rates of referral and testing included age, histology, history of oral contraceptive use, and family history of ovarian cancer.  Prior health care utilization indicators did not affect genetic referral or testing.”

“Univariable and multivariable analyses were used to assess predictors of referral and genetic consultation in the cohort prior to gynecologic oncologist-initiated BRCA testing (2004-2016). The presence of a primary care physician, continuity of care, and prior breast or cervical cancer screening (predictors of Health care utilization) did not influence referral rate for genetics consultation; 92.2% of patient in the 2004-2013 cohort and 88.1% in the 2014-2016 cohort had a primary care physician (Table 2). Factors shown to be associated with genetic consultation on multivariable analysis included age (P < 0.002), histology (P <0.005), history of oral contraceptive use (P =0.049) and a family history of EOC (P =0.007) (Appendix 1). As shown in Figures 2, the effect of age is more pronounced in the 2004-2013 period (Figure 2A) compared to the 2014-2016 cohort (Figure 2B), with referral rates decreasing more rapidly with increasing age.”

To further investigate secondary factors and the influence on genetic testing the authors feel a qualitative study would be required.  Qualitative analysis was not part of this research study, so no further conclusions can be drawn from these data beyond hypothesis generation and what has already been indicated in the manuscript. 

A simple summary has been added to the manuscript:

"This study was performed to better understand rates and factors that influence patients in accepting a referral to genetics, or testing for genes that predispose them to ovarian cancer (BRCA1/2).   Using multiple provincial databases and registries, the study team looked at data from 944 patients with high grade ovarian cancer between 2004-2019.  We found that the rate of genetic referrals fluctuated over time, however the rate of genetic testing increased over the entire timeframe.  Factors found to increase rates of referral and testing included age, cancer histology, history of oral contraceptive use, and family history of ovarian cancer.  Increasing the rate of genetic testing will help patients and their health care team plan clinical management and treatment."