Pattern Anlysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Review “Analysis of the patterns of risk-reducing strategies of Korean unaffected BRCA1/2 mutation carriers”, Dabin Kim et al. curroncol-3234139

In this study, Kim et al. explore cancer surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. Key findings include: 1) BRCA1/2 mutation carriers face a significantly increased risk of breast and ovarian cancer, yet data on their interventions are limited; 2) Among 46 surveyed carriers, ten developed breast cancer, one had ovarian cancer, and three had other cancers; 3) Only 19.4% underwent the recommended annual breast cancer surveillance, none had ovarian or prostate cancer surveillance, and 9.7% utilized chemoprevention. Additionally, only one participant underwent risk-reducing salpingo-oophorectomy. The authors emphasize that these low rates of surveillance and intervention highlight the need for strategies to encourage greater participation in risk reduction. This is a meaningful prospective study, although it has limitations related to data availability and the small sample size. The main criticism of this study is that it is primarily descriptive, only addressing surveillance rates with limited data on interventions. It could not provide answers on whether cancer surveillance and preventive interventions are effective in reducing breast cancer incidence or delaying its progression.

Figure 4: The green bar should be labeled "at least once" instead of "more than once," in accordance with the author's text.

Comments on the Quality of English Language

The English language requires extensive editing. Below are a few examples:

The title is wordy and awkwardly structured. It can be refined to: "Pattern Analysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers."

Lines 36-37: Modify "BRCA1/2 genes are tumor suppressor genes that play a critical role in repairing DNA damage and maintaining the double-stranded structure of DNA" to "BRCA1 and BRCA2 are tumor suppressor genes that play a critical role in repairing DNA damage and maintaining the integrity of double-stranded DNA" to avoid repetition and improve clarity.

Line 92: Consider using "has been limited" instead of "was limited" to maintain consistency with the ongoing nature of the data collection issue.

Lines 103-104: Rephrase "We conducted nine follow-up telephone surveys between August 2016 and December 2020 with the 46 unaffected BRCA1/2 mutation carriers" to "We conducted nine follow-up telephone surveys from August 2016 to December 2020 among 46 unaffected BRCA1/2 mutation carriers" for better flow.

Author Response

Comments and Suggestions for Authors

Review “Analysis of the patterns of risk-reducing strategies of Korean unaffected BRCA1/2 mutation carriers”, Dabin Kim et al. curroncol-3234139

In this study, Kim et al. explore cancer surveillance and risk-reducing interventions among unaffected BRCA1/2 mutation carriers. Key findings include: 1) BRCA1/2 mutation carriers face a significantly increased risk of breast and ovarian cancer, yet data on their interventions are limited; 2) Among 46 surveyed carriers, ten developed breast cancer, one had ovarian cancer, and three had other cancers; 3) Only 19.4% underwent the recommended annual breast cancer surveillance, none had ovarian or prostate cancer surveillance, and 9.7% utilized chemoprevention. Additionally, only one participant underwent risk-reducing salpingo-oophorectomy. The authors emphasize that these low rates of surveillance and intervention highlight the need for strategies to encourage greater participation in risk reduction. This is a meaningful prospective study, although it has limitations related to data availability and the small sample size. The main criticism of this study is that it is primarily descriptive, only addressing surveillance rates with limited data on interventions. It could not provide answers on whether cancer surveillance and preventive interventions are effective in reducing breast cancer incidence or delaying its progression.

• Thank you very much for recognizing the value of our study. We acknowledge your criticism of the study’s limited power. In this study, our goal was to determine whether unaffected BRCA1/2 mutation carriers were carrying risk-reducing strategies as recommended by the guidelines. While we could identify the onset of primary cancer among the unaffected carriers, we could not obtain detailed information regarding cancer stage or prognosis. As a result, we were unable to conclude whether intensive surveillance could lead to early detection, but our findings highlight the critical need for unaffected carriers to actively participate in risk-reducing strategies.

Figure 4: The green bar should be labeled "at least once" instead of "more than once," in accordance with the author's text.

• Thank you for your detailed comment. We’ve revised our figure 4 as you’ve mentioned, and changed more than once to at least once.

Comments on the Quality of English Language

The English language requires extensive editing. Below are a few examples:

The title is wordy and awkwardly structured. It can be refined to: "Pattern Analysis of Risk-Reducing Strategies in Unaffected Korean BRCA1/2 Mutation Carriers."

Lines 36-37: Modify "BRCA1/2 genes are tumor suppressor genes that play a critical role in repairing DNA damage and maintaining the double-stranded structure of DNA" to "BRCA1 and BRCA2 are tumor suppressor genes that play a critical role in repairing DNA damage and maintaining the integrity of double-stranded DNA" to avoid repetition and improve clarity.

Line 92: Consider using "has been limited" instead of "was limited" to maintain consistency with the ongoing nature of the data collection issue.

Lines 103-104: Rephrase "We conducted nine follow-up telephone surveys between August 2016 and December 2020 with the 46 unaffected BRCA1/2 mutation carriers" to "We conducted nine follow-up telephone surveys from August 2016 to December 2020 among 46 unaffected BRCA1/2 mutation carriers" for better flow.

• Thank you for your meticulous feedback for improvement of our manuscript. We’ve made some changes on our English manuscript based on your comments and underwent additional English editing with MDPI English editing service.

 

Reviewer 2 Report

Comments and Suggestions for Authors

This paper explores patterns surveillance and risk reduction interventions in a cohort of Korean individuals who carry deleterious mutations in BRCA 1 or BRCA 2.  The research  methods are valid and carefully explained, but  significant drawbacks to the study are that this is a retrospective survey analysis on a very small sample of participants ( 46 total of 192 contacted)  of which 15 male and 31 female, with very young median age of participants. This skews to a lower probability of cancer diagnoses compared to other cohorts of BRCA mutation carriers.  Most of the individuals did not undergo screening as per NCCN guidelines for BRCA mutation carriers. No patients underwent risk-reducing bilateral mastectomies and only 1 female had prophylactic BSO. 

The interesting conclusions from this inquiry is that in Korea there may be specific cultural and systemic reasons for why Koreans with BRCA mutations do not undergo screening or risk-reducing surgeries. Notably that insurance does not cover cost of MRI tests. Most respondents who did undergo screening did so because of fear of cancer, advice from an affected family member.  For those who did not undergo screening the reasons were lack of access and high cost, fear of cancer diagnosis and lack of knowledge about cancer risk. 

These are important points regarding how to design and implement culturally sensitive and practical screening/surveillance programs for individuals with hereditary cancer syndromes. More general education, better access to medical facilities with well designed high risk clinics./surveillance programs, and insurance coverage for screening tests are very important - not only in Korea - but everywhere. 

The authors do a good job in emphasizing these points in their conclusions. It would have been a more powerful paper if the sample size were larger and included individuals at older ages. This point should be added to the conclusion. Older individuals have higher risk of developing cancer, might have more access to health care system and might be more concerned than younger individuals about cancer diagnosis. 

Author Response

Comments and Suggestions for Authors

This paper explores patterns surveillance and risk reduction interventions in a cohort of Korean individuals who carry deleterious mutations in BRCA 1 or BRCA 2. The research methods are valid and carefully explained, but significant drawbacks to the study are that this is a retrospective survey analysis on a very small sample of participants (46 total of 192 contacted) of which 15 male and 31 female, with very young median age of participants. This skews to a lower probability of cancer diagnoses compared to other cohorts of BRCA mutation carriers.  Most of the individuals did not undergo screening as per NCCN guidelines for BRCA mutation carriers. No patients underwent risk-reducing bilateral mastectomies and only 1 female had prophylactic BSO. 

The interesting conclusions from this inquiry is that in Korea there may be specific cultural and systemic reasons for why Koreans with BRCA mutations do not undergo screening or risk-reducing surgeries. Notably that insurance does not cover cost of MRI tests. Most respondents who did undergo screening did so because of fear of cancer, advice from an affected family member.  For those who did not undergo screening the reasons were lack of access and high cost, fear of cancer diagnosis and lack of knowledge about cancer risk. 

These are important points regarding how to design and implement culturally sensitive and practical screening/surveillance programs for individuals with hereditary cancer syndromes. More general education, better access to medical facilities with well designed high risk clinics./surveillance programs, and insurance coverage for screening tests are very important - not only in Korea - but everywhere. 

The authors do a good job in emphasizing these points in their conclusions. It would have been a more powerful paper if the sample size were larger and included individuals at older ages. This point should be added to the conclusion. Older individuals have higher risk of developing cancer, might have more access to health care system and might be more concerned than younger individuals about cancer diagnosis. 

• Thank you very much for your positive feedback and for recognizing the significance of our research as the first in Korea to actively follow up with healthy BRCA carriers and assess the incidence of breast and ovarian cancers. We fully agree with your opinion on our study’s limitation regarding small sample size and relatively young age of included carriers. We’ve revised some sentences in our 10^th paragraph of Discussion section (lines 296-302) to clarify the distinct limitation of our study. We hope to have further research involving a larger number of BRCA carriers, especially within an older age group. We appreciate your thoughtful input and will consider this direction for future studies.