High rate of occult cancer found in prophylactic mastectomy specimens despite thorough presurgical assessment with MRI and ultrasound: findings from the Hereditary Breast and Ovarian Cancer Registration 2016 in Japan.

PURPOSE: Prophylactic surgery is a preemptive strategy for hereditary breast and ovarian cancer (HBOC). Prophylactic mastectomy (PM) reduces breast cancer risk by > 90%. The aim of our study is to analyze the information of the Japanese pedigrees and to utilize the results for clinical practice. METHODS: We statistically analyzed records of HBOC registrees who had undergone BRCA1/2 genetic testing at seven medical institutions up until 2016. In the cases of PM, we examined breasts with the use of mammography (MMG), ultrasound (US), and magnetic resonance imaging (MRI) before surgery. After PM, the specimens were divided about 1 cm serially and examined in their entirety. RESULTS: Of 1527 registrees who underwent BRCA testing, 1125 (73.7%) were negative for BRCA1/2 mutation, 297 (19.5%) were positive for BRCA1/2 mutation (BRCA1/2MUT+), and 105 (6.9%) had uncertain results. To decide whether to undergo total mastectomy vs. breast-conserving surgery (BCS), 370 registrees underwent presurgical genetic testing. During the follow-up period, four new-onset breast cancers were found among the 55 non-affected BRCA carriers. Among the 73 BRCA1/2MUT+ carriers who underwent BCS, 3 were found to have ipsilateral breast cancer. Of 189 BRCA1/2MUT+ carriers with unilateral breast cancer, 8 were found to have contralateral breast cancer. Of 53 PM specimens, 6 (11.3%) were found to have occult breast cancer despite using MMG, US, and MRI. CONCLUSIONS: Our report showed a relatively higher incidence rate of occult cancer at 11.3% in PM specimens despite thorough pre-operative radiological evaluations, which included a breast MRI. Considering the occult cancer rates and the various pathological methods of our study and published studies, we propose the necessity of a histopathological protocol.

Cost-effectiveness of surveillance and prevention strategies in BRCA1/2 mutation carriers.

BACKGROUND: Cost-effectiveness analysis is an important aspect of healthcare, including in Japan, where preventive measures for BRCA1/2 mutation carriers are not covered by health insurance. METHODS: We developed Markov models in a simulated cohort of women aged 35-70 years, and compared outcomes of surveillance with risk-reducing mastectomy (RRM) at age 35, risk-reducing salpingo-oophorectomy (RRSO) at age 45, and both (RRM&RRSO). We used breast and ovarian cancer incidences and adverse event rates from the previous studies, adjuvant chemotherapy, and hormonal therapy rates from the Hereditary Breast and Ovarian Cancer Registration 2015 in Japan, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology, and Ministry of Health, Labour and Welfare, and direct costs from St. Luke's International Hospital and Keio University Hospital. We used previously published preference ratings of women without known high risk to adjust survival for quality of life. The discount rate was 2%. RESULTS: Compared with surveillance, RRSO and RRM&RRSO were dominant (both cost-saving and more effective), and RRM was cost-effective in BRCA1 mutation carriers, while RRM and RRM&RRSO were dominant and RRSO was cost-effective in BRCA2. Among the four strategies including surveillance, RRM&RRSO and RRM were the most cost-effective in BRCA1 and BRCA2 mutation carriers, respectively. CONCLUSIONS: With quality adjustment, RRM, RRSO, and RRM&RRSO were all cost-effective preventive strategies in BRCA1/2 mutation carriers, with RRM&RRSO being the most cost-effective in BRCA1 and RRM in BRCA2. This result supports the inclusion of insurance coverage for BRCA mutation carriers in Japan.

Social impacts of the work loss in cancer survivors.

BACKGROUND: As cancer frequently occurs during the most productive years of life, our purpose was to estimate the cost of work loss of cancer survivors and develop interventions to minimize the loss. METHODS: We estimated the cost of the work loss from all cancers resulting from patients' inpatient, outpatient, and non-treatment days. This was calculated with a new method, the product of the "employment rate coefficient × productivity coefficient," making use of data published by the Japanese Ministries. RESULTS: The estimate of work loss on treatment days for all cancers was $1820.21 million in men and $939.38 million in women. In terms of disease classification, lung cancer was the largest cause in men, whereas breast cancer was the largest in women. On non-treatment days, the work losses because of gastric, colon, and lung cancers were large in men, while breast cancer was the largest in women and in total. The estimated loss for all cancers was $3685.506 million in men and $2502.565 million in women, when the product was assumed 0.5. CONCLUSIONS: In Japan, breast cancer was considered the leading cause for cost of work loss, and the most influential cause when the product of the "employment rate coefficient × productivity coefficient" for breast cancer was assumed the same as the product for all other types of cancers. It is necessary to establish support systems for working cancer survivors.

Societal cost-effectiveness analysis of the 21-gene assay in estrogen-receptor-positive, lymph-node-negative early-stage breast cancer in Japan.

BACKGROUND: Breast-cancer incidence and mortality have been increasing in Japan. Japanese-specific clinical validity and utility data for the 21-gene assay (Oncotype DX® Breast Cancer Assay; Genomic Health, Inc., Redwood City, USA) are now available. The objective of this study was to evaluate the cost-effectiveness of the 21-gene assay for the guidance of adjuvant chemotherapy decisions in estrogen-receptor-positive, lymph-node-negative, early-stage breast cancer patients, from the Japanese societal perspective. METHODS: The recurrence risk group distribution by the 21-gene assay result and the assay's influence on adjuvant chemotherapy recommendations were obtained from a study of 104 patients. A state-transition cohort (Markov) model tracked time from surgery until distant recurrence and from distant recurrence to death. Adjuvant chemotherapy benefit by 21-gene assay risk group was based on published clinical validation studies. Direct and indirect medical costs were obtained from the referral centers. Utilities associated with progression and chemotherapy-related adverse events were extracted from literature. Sensitivity analyses assessed the key drivers and robustness of the primary outcomes. RESULTS: The 21-gene assay identified 48% of patients as low-risk, 36% as intermediate-risk, and 16% as high-risk. Total acute chemotherapy-related costs decreased by ¥154,066 due to less adjuvant chemotherapy usage. In the high-risk group, adjuvant chemotherapy use increased 18%, leading to survival benefits. Chemotherapy use overall decreased by 19%. Monitoring costs increased by ¥3,744 but recurrence costs declined by ¥46,113 per patient. Use of the 21-gene assay increased quality-adjusted-life-years (QALYs) by 0.241 per patient on average; the net cost per QALY gained was ¥636,752 ($6,368). CONCLUSIONS: The 21-gene assay for women with estrogen-receptor-positive, lymph-node-negative, early-stage breast cancer is projected to be cost-effective in Japan.

Pathological assessment of microinvasive carcinoma of the breast.

BACKGROUND: Microinvasive breast cancer (T1mi) is considered as a precursor of invasive cancer developing from ductal carcinoma in situ (DCIS). This study discussed the clinicopathological and immunohistochemical features of T1mi by comparing those of ductal carcinoma in situ (Tis) and T1a to assess the nature and causes of the progression of Tis into invasive cancer. METHODS: Three hundred and ninety-two Tis, 32 T1mi, and 141 T1a lesions which were pathologically diagnosed in surgical specimens between 2006 and 2009 were analyzed retrospectively. T1mi was defined as a tumor no greater than 1 mm in its greatest dimensions, and T1a was defined as a tumor larger than 1 mm but no greater than 5 mm. RESULTS: The frequency of the comedo type was significantly higher in T1mi (68.8%) than in Tis (13.8%) (p < 0.001) and T1a (30.5%) (p < 0.001). Estrogen receptor (ER) negative-HER2 positive type was more frequent in T1mi (46.9%) than in Tis (8.7%) (p < 0.001) and T1a (10.6%) (p < 0.001). There was a significant difference in Ki-67 index between T1mi (35.2 ± 19.2%) and Tis (18.8 ± 14.5%) (p < 0.001). T1mi had higher rates of comedo type and ER negative-HER2 positive type. CONCLUSION: Comedo type and ER negative-HER2 positive type were found more frequently in T1mi than in Tis and T1a. There could be different biological mechanisms for promoting Tis into invasive cancer from enlarging invasive cancer.