In gBRCA1/2-positive variant carriers, RRSO has been confirmed to reduce the risk of developing cancer and prolongs overall survival [5, 8,9,10,11,12,13]. Risk-reducing surgery not only contributes to lower mortality in HBOC patients, but also has a clinically significant impact in reducing the fear of future cancer [14]. In Japan, with the April 2020 Physician Fee Review, certain breast cancer patients and all ovarian cancer patients have become able to receive the BRACAnalysis test (Myriad Genetics) as a part of covered medical treatment [4, 5]. In addition, RRSO and RRM are covered for gBRCA1/2-positive breast and ovarian cancer patients [4, 6], and surveillance MRI of the breast is also covered for gBRCA1/2-positive breast and ovarian cancer patients not undergoing risk-reducing surgery [4]. As of the end of 2022, about 200 cases of genetic counseling for HBOC have been performed in our hospital. BRCA1/2 genetic testing was performed in approximately 160 cases, with the pathogenic variant found in 20 cases. More than 80% of tests have been performed in the period since insurance coverage was approved. We have also performed 8 RRSOs in our hospital. In all cases of RRSO performed, breast cancer was already present (Table 1). The number of RRSO and RRM procedures performed has increased since coverage by health insurance was obtained.

Specifically for RRSO, we work with the Department of Obstetrics and Gynecology to ensure that RRSO is performed within one year of HBOC diagnosis. If CRRM and RRSO can be performed at the same time as breast cancer treatment, many patient anxieties can be expected to be alleviated. However, close cooperation with the Department of Obstetrics and Gynecology and Department of Anesthesiology is necessary, and addressing multiple issues simultaneously is challenging. In the present case, after discussion with our Department of Obstetrics and Gynecology, we were able to perform all surgeries on the same day. On reflection, the surgery took somewhat longer than usual for this type of surgery. Currently, bilateral mastectomies are performed by one surgeon at our hospital, but if two surgeons could perform bilateral mastectomies at the same time, operation time could be reduced. We will continue to consider other ways to shorten operation time, both in terms of technique and operating room environment. The average hospital stay after breast surgery in Japan tends to be longer than in Western countries. As such, we will also consider ways to promote earlier discharge from hospital.

Generally, advanced ovarian cancer has a poor prognosis. In particular, HBOC-related ovarian cancer is often advanced at the time of diagnosis and shows poor prognosis [15, 16]. Previous reports have shown that ovarian cancers associated with gBRCA pathogenic variants exhibit distinct clinical behaviors, including advanced stage (International Federation of Gynecology and Obstetrics (FIGO) stages III–IV [17]), papillary, high-grade serous, and poorly differentiated adenocarcinoma. As a result, performing risk-reducing surgery for HBOC cases in which ovarian cancer has not yet developed can significantly impact life prognosis. Risk-reducing surgery can thus be considered cancer-preventive medicine in the true sense of the term. However, in Japan, risk-reducing surgery is not covered by health insurance for patients without cancer [7]. At our hospital, CRRM costs about $4,200 USD (including tax), RRSO costs about $6,000 USD (including tax), and hysterectomy and ovarian salpingectomy costs about $8,300 USD (including tax). More than ever, we are calling for the extension of HBOC insurance coverage for people who have not yet developed cancer.

The patient in this case had been undergoing surveillance at her own expense since she had been found to be gBRCA2-positive, due to concerns about developing ovarian cancer. While the National Comprehensive Cancer Network (NCCN) guidelines recommend risk-reducing surgery for gBRCA1/2-positive variant carriers, they do not recommend ovarian surveillance. This is because no evidence suggests that such surveillance has any impact in reducing the risk of developing, or dying from, cancer. However, because the patient had not developed cancer, she would have had to pay out-of-pocket for any tests or risk-reducing surgeries. She was therefore reluctant to undergo risk-reducing surgery because of the high cost, and chose instead to undergo breast and ovarian surveillance rather than risk-reducing surgery. Surveillance and testing led to a diagnosis of non-invasive breast cancer, at which time both breast cancer surgery and risk-reducing surgery were covered by the Japanese health insurance system. Because few changes were evident on imaging and only slight changes in the kinetic curve were seen on contrast-enhanced MRI of the breast, we might not have considered core needle biopsy in the absence of a background of pathogenic mutations in gBRCA2. After the surgery, the patient was very satisfied because she had been able to undergo surgery for the cancer and RRSO and CRRM at the same time. Because this was before any ovarian cancer developed, she was able to undergo laparoscopic surgery and felt very well after the surgery. The patient has an adult daughter who does not want to be tested for BRCA1/2. In the past, she had left it up to her daughter to decide whether to undergo BRCA1/2 testing, but now that she has undergone this surgery, she is actively encouraging her daughter to undergo testing. If tested, her daughter would know her own susceptibility and could better plan for her healthcare. If she discovers she has a BRCA2 pathogenic variant that had been identified in her mother, close surveillance might detect early breast and ovarian cancer. Even with these benefits, however, cancer-free individuals may be reluctant to be tested for BRCA1/2 if surveillance and risk-reducing surgery must be self-funded. Unfortunately, this is the current state of HBOC medicine in Japan.

In conclusion, we encountered a case of HBOC in which both RRSO and RRM were performed simultaneously in addition to breast cancer treatment at the request of the patient. When HBOC was diagnosed, the patient was concerned about developing ovarian cancer, but since she had not developed cancer, the cost of risk-reducing surgery was very high. This was therefore a case in which risk-reducing surgery could not be performed. We believe that extending insurance coverage for HBOC cases to those patients who have not yet developed cancer represents an extremely important issue for true cancer-preventive medicine in the future. In addition, if risk-reducing surgery is not covered by insurance because no cancer has yet developed, the key issue is how to detect cancer early and prevent a life-threatening status through regular surveillance performed at personal expense. To improve the accuracy of breast and ovarian surveillance, collaboration needs to be strengthened between breast oncologists and specialists with sufficient expertise in contrast-enhanced MRI of the breast and gynecologic oncologists, to create a safe environment not only for cancer patients, but also for cancer-free HBOC individuals.