実臨床における乳癌既発症例に対するBRCA遺伝学的検査の現状と 臨床病理学的因子に関する検討

に若年の Triple Negative タイプでは，家族歴がない場合で

1 ）Easton D.F‚ Pharoah P.D.P‚ Antoniou A.C‚ et al. ： Gene-

も BRCA 遺伝子病的バリアントの陽性率が高い16）．我々

panel sequencing and the prediction of breast-cancer risk.

の検討でも家族歴のない症例のうち 2 例（18．2%）で

N Engl J Med‚ 372：2243-2257‚ 2015.

BRCA 遺伝子病的バリアント陽性であり，いずれも Triple

2 ）Momozawa Y‚ Iwasaki Y‚ Parsons M.T et al.： Germline

Negative タイプであった．このような症例では，保険適

pathogenic variants of 11 breast cancer genes in 7‚051

32

実臨床における BRCA 遺伝学的検査の現状

Japanese patients and 11‚241 controls. Nat Commun‚ doi：

predictors of BRCA1 and BRCA2 mutation in a

10.1038/s41467-018-06581-8.

population-based study of breast cancer in white and

3 ）遺伝性乳癌卵巣癌症候群（HBOC）診療の手引き2017

年版．

「わが国における遺伝性乳癌卵巣癌の臨床遺伝

black American women ages 35 to 64 years. Cancer Res‚

66：8297-8308‚ 2006.

的特徴の解明と遺伝子情報を用いた生命予後の改善

12）O Shaughnessy J‚ Brezden-Masley C‚ Cazzaniga M‚ et al.：

に関する研究」班（編）

，36-41，金原出版，2017．

Prevalence of germline BRCA mutation in HER2-

4 ）坂東裕子：PARP 阻害薬（BRCA 関連乳癌，遺伝性乳

negative metastatic breast cancer：global results from the

癌卵巣癌症候群）

．内分泌外会誌，36：107-111，2019．

5 ）Kuchenbaecker KB‚ Hopper JL‚ Barnes DR‚ et al.： Risks

real-world‚ observational BREAKOUT study. Breast

Cancer Res‚ 22：114‚ 2020.

of breast‚ ovarian‚ and contralateral breast cancer for

13）Sugano K‚ Nakamura S‚ Ando J‚ et al.： Cross-sectional

BRCA1 and BRCA2 mutation carriers. JAMA‚ 317：

analysis of germline BRCA1 and BRCA2 mutations in

2402-2416‚ 2017.

Japanese patients suspected to have hereditary breast/

6 ）Muller D‚ Danner M‚ Rhiem K‚ et al.： Cost-effectiveness

of different strategies to prevent breast and ovarian

cancer in German women with a BRCA 1 or 2 mutation.

Eur J Health Econ‚ 19：341-353‚2018.

ovarian cancer. Cancer Sci‚ 99：1967-1976‚ 2008.

14）福富隆志：遺伝性／家族性乳癌（遺伝性乳癌・卵巣

癌を含む）．家族性腫瘍，14：15-20，2014．

15）Arai M‚ Yokoyama S‚ Watanabe C‚ et al.： Genetic and

7 ）遺伝性乳癌卵巣癌（HBOC）診療ガイドライン2021

clinical characteristics in Japanese hereditary breast and

年度版．日本遺伝性乳癌卵巣癌総合診療制度機構

ovarian cancer：first report after establishment of HBOC

（編），42-47，86-91，金原出版，2021．

8）

“NCCN guidelines for Genetic/Familial High-Risk

Assessment”

. https：//www.nccn.org/professionals/

registration system in Japan. Journal of Human Genetics‚

63：447-457‚ 2018.

16）野水 整，松嵜正實，片方直人，他：家族性乳癌に

physician_gls/pdf/genetics_bop.pdf‚（accessed 2021-10-

おける BRCA 遺伝子診断と臨床病理学的検討．日臨

09）

外雑誌，75：1765-1771，2014．

9 ）Curigliano G‚ Burstein HJ‚ Winer EP‚ et al.：De-escalating

17）栃久保順平，細川優子，森 克昭，他：当院で乳が

and escalating treatments for early-stage breast cancer：

ん患者に新しく導入したがん家族歴問診票の有用性

the St. Gallen International Expert Consensus Conference

の検討．遺伝性腫瘍，21：7-11，2021．

on the Primary Therapy of Early Breast Cancer 2017.

Ann Oncol‚ 28：1700-1712‚ 2017.

10）Allison KH‚ Hammond EH‚ Dowsett M‚ et al.： Estrogen

and Progesterone Receptor Testing in Breast Cancer：

ASCO/CAP Guideline Update. J Clin Oncol‚ 38： 13461366‚ 2020.

11）Malone KE‚ Daling JR‚ Doody DR‚ et al.：Prevalence and

18）Davey MG‚ Davey CM‚ Ryan EJ‚ et al.：Combined breast

conservation therapy versus mastectomy mutation

carriers- A systematic review and meta-analysis. The

Breast‚ 56：26-34‚ 2021.

19）日本乳癌学会．

“乳癌診療ガイドライン”

jbcs.xsrv.jp/guidline/2018/index/ekigakuyobo/cq6（参照

2021-01-15）

33

原 田 郁，他

Abstract

CLINICOPATHOLOGICAL OUTCOME OF BRCA GENETIC

TESTING IN BREAST CANCER:

A SINGLE INSTITUTION’S EXPERIENCE

Fumi HARADA 1 ）, Takashi CHISHIMA 1 ）, Shinya YAMAMOTO 1 , 3 ）,

Yukako SHIBATA 1 ）, Hideki TAKEUCHI 1 ）, Shiori INOUE 1 ）,

Hitoshi ARIOKA 2 ）, Itaru ENDO 4 ）

1）

Department of Breast Surgery, Yokohama Rosai Hospital

2）

Department of Pathology, Yokohama Rosai Hospital

3）

4）

Department of Breast and Thyroid Surgery, Yokohama City University Medical Center

Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine

Introduction: BRCA genetic testing was approved as a companion diagnostic for metastatic breast cancer in June,

2018 in Japan. The approval has been expanded since April, 2020. This study reviewed the clinicopathological

features of patients undergoing BRCA genetic testing in a single institution. Materials and Methods: The

clinicopathological records of 49 consecutive patients who underwent BRCA genetic testing for breast cancer from

June, 2018 to December, 2020 were retrospectively reviewed. The testing was suggested in accordance with the

NCCN guideline and the Japanese guideline for diagnosis and treatment of HBOC. Results: The median age at

diagnosis of breast cancer was 47 years. Three patients (6.1%) had multiple primary breast cancers. Twenty-four

patients (48.9%) had a family history of breast cancer within third-degree relatives. BRCA pathogenic variant was

identified in 11 patients (22.4%), with BRCA1 in 5 patients and BRCA2 in 6 patients. VUS was not identified. Four

(80.0%) of 5 patients with BRCA1 pathogenic variant had triple-negative breast cancer. Four (66.6%) of 6 patients

with BRCA2 pathogenic variant had luminal breast cancer. The rate of a family history of breast cancer within thirddegree relatives was significantly higher in patients with BRCA pathogenic variant than in patients without the

variant (81.8% vs. 39.5%, p=0.018). Conclusion: A family history of breast cancer within third-degree relatives is

an important factor for recommending BRCA testing.

34

...