breast cancer

Japanese: 乳癌

Definition/Concept The mammary gland is a type of sweat gland tissue, and is a functional organ whose purpose is to provide nutrition and immunity to newborns through milk. Malignant tumors that develop in this mammary gland tissue are called breast cancer. "Breast cancer" refers to all malignant tumors of the breast, including sarcomas. In the narrow sense, "breast cancer" refers only to epithelial malignant tumors (carcinomas).
ClassificationTumors that occur in the breast are classified as epithelial tumors, non-epithelial tumors, or mixed tumors (Table 12-19-1). Breast cancer is an epithelial malignant tumor, and is broadly divided into non-invasive carcinoma and invasive carcinoma. Non-invasive carcinoma is divided into ductal carcinoma in situ and lobular carcinoma in situ. Invasive carcinoma is classified into conventional invasive ductal carcinoma and special types. Conventional invasive ductal carcinoma accounts for approximately 90% of invasive cancers, and in Japan it is further subdivided into nipple-ductal carcinoma, solid-ductal carcinoma, and scirrhous carcinoma depending on the pattern of invasion and degree of differentiation. Approximately 5% are lobular carcinoma.Paget's disease of the breast is a subtype of breast cancer characterized by intraepidermal progression of the nipple and areola.
Causes and EtiologyThe risk of developing breast cancer includes those related to increased female hormones and extended exposure periods, such as early menarche, late menopause, few births or breastfeeding experiences, postmenopausal obesity, and postmenopausal hormone replacement therapy, as well as hereditary factors such as a family history or personal history of breast cancer and abnormalities in the BRCA1/2 gene.Other factors include radiation exposure, a history of proliferative breast disease, high birth weight, alcohol, and smoking history.
Epidemiology: In Europe and the United States, both the incidence and mortality rates are on the decline, but in Japan the incidence rate has increased five-fold over the past 30 years, and the mortality rate is also on the rise. Among cancers in women, it is the number one cause of incidence and the fifth most common cause of mortality (as of 2009). Compared to cancers of other organs, it is characterized by its tendency to develop at a younger age, with the most common age of onset being the late 40s and the most common age of death being the early 60s. Breast cancer can also occur in men, and the male to female incidence ratio is said to be approximately 1:100.
Clinical symptoms: Most patients visit the hospital because of a breast lump, but other symptoms such as breast pain and abnormal nipple discharge or erosion are also reasons for visits. Breast pain is not necessarily related to the presence of breast cancer. In advanced breast cancer, symptoms such as indentation of the skin over the tumor, edema, redness, and ulcer formation may be observed. There may also be only swollen lymph nodes in the armpits, or no palpable tumor in the breast but the lesion can only be detected by imaging tests.
The presence of intramammary lesions is diagnosed by visual and palpable examination, mammography (Figure 12-19-1), breast ultrasound (Figure 12-19-2A), breast MRI, etc. Definitive diagnosis requires pathological examination, such as fine needle aspiration cytology, secretion cytology, needle biopsy, and aspiration breast tissue biopsy. Even in the case of microcalcified lesions that can be identified by mammography alone, a definitive diagnosis can be made by performing a biopsy under mammography guidance. CT scans, bone scintigraphy, FDG-PET scans, etc. are performed to search for distant metastasis. Blood tumor markers that increase in breast cancer include CEA and CA15-3. They are rarely elevated at the time of diagnosis except in advanced cancers accompanied by distant metastasis.
In molecular biological diagnosis, breast cancer is classified as hormone receptor positive or negative depending on the presence or absence of estrogen receptor (ER) and progesterone receptor (PgR) expression in breast cancer tissue. In addition, breast cancer is classified as HER2 positive or negative depending on the presence or absence of human epidermal growth factor receptor type 2 (HER2).
The differential diagnosis would be the neoplastic lesions of the breast listed in Differential Diagnosis Table 12-19-1. Intraductal papilloma, fibroadenoma, and fibrocystic mastopathy, which is a localized proliferative change in normal milk ducts, are included in the differential diagnosis. In addition, phyllodes tumors (benign and malignant) and sarcomas (malignant) should also be kept in mind as lesions that have a strong tendency to grow as a mass.
Treatment involves a combination of therapeutic and preventive surgical therapy, radiation therapy, and drug therapy. Surgical therapy consists of surgery on the breast and axilla, and either partial mastectomy or mastectomy is performed depending on the size and spread of the primary tumor. For the axilla, a sentinel lymph node biopsy and axillary dissection are performed depending on the state of metastasis to the lymph nodes. After partial mastectomy, radiation therapy is performed on the remaining breast, and in cases of advanced lymph node metastasis, radiation therapy is performed on the chest wall and regional lymph nodes.
Systemic drug therapies include chemotherapy (anthracyclines, taxanes, etc.), hormone therapy, and molecular targeted therapy. Hormonal therapy with tamoxifen and aromatase inhibitors can be expected to be effective for hormone receptor-positive breast cancer. These hormone therapy drugs not only have a therapeutic effect, but also have the effect of preventing the development of new breast cancer. For HER2-positive breast cancer, anti-HER2 therapy drugs such as trastuzumab and lapatinib are selected as molecular targeted therapies. Drug therapy is the main treatment for distant metastatic lesions (bones, soft tissues, lungs, liver, brain, etc.), but radiation therapy may also be performed depending on the condition.
The 5-year relative survival rate for cases diagnosed between 1997 and 2000 at facilities affiliated with the National Cancer (Adult Disease) Center Council was 98.2% for stage I, 91.5% for stage II, 67.8% for stage III, and 31.5% for stage IV, for an overall rate of 87.3%. [Saji Shigehira and Toi Masakazu]
■ References <br /> Kyoto University Graduate School of Medicine, Department of Surgery: Surgical Training Manual, 2nd ed., pp327-347, Nankodo, Tokyo, 2009.
Edited by the Japanese Breast Cancer Society: Breast Oncology, pp11-68, Kanehara Publishing, Tokyo, 2012.
Edited by the Japanese Breast Cancer Society: Breast Cancer Guidelines, Clinical and Pathological, 17th Edition, pp22-34, Kanehara Publishing, Tokyo, 2012.

Table 12-19-1
Tumors in the Breast (Kyoto University Graduate School of Medicine, Department of Surgery, 2009)

Table 12-19-1

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

定義・概念
　乳腺は汗腺組織の1つであり，新生児に乳汁を通じて栄養や免疫力を与えることを目的とする機能臓器である．この乳腺組織に発生した悪性腫瘍を乳がん（breast cancer）という．“乳がん”は肉腫などを含むすべての乳腺悪性腫瘍を示す．“乳癌”は狭義には上皮性悪性腫瘍（癌腫，carcinoma）のみを指す．
分類
　乳腺に発生する腫瘍は上皮性腫瘍，非上皮性腫瘍，それらの混合腫瘍に分類される（表12-19-1）．乳癌は上皮性悪性腫瘍であり，非浸潤癌と浸潤癌に大別される．非浸潤癌は非浸潤性乳管癌と非浸潤性小葉癌に分けられる．浸潤癌は通常型の浸潤性乳管癌と特殊型に分類される．通常型浸潤性乳管癌は浸潤癌の約90％を占め，わが国では浸潤様式，分化度によってさらに乳頭腺管癌，充実腺管癌，硬癌に細分類される．約5％が小葉癌である．乳房Paget病（Paget’s disease）は乳頭・乳輪部の表皮内進展を特徴とする乳癌の一亜型である．
原因・病因
　乳癌の罹患リスクには，早い初潮，遅い閉経，少ない出産・授乳経験，閉経後の肥満，閉経後のホルモン補充療法など，女性ホルモンの増加や暴露期間延長に関連するものと，乳癌の家族歴・既往歴，BRCA1/2遺伝子の異常など遺伝性関連のものがある．また，放射線被曝，増殖性乳腺疾患の既往，生下時体重が重い，アルコール，喫煙歴などいくつかの因子があげられる．
疫学
　欧米では罹患率，死亡率ともに減少傾向であるが，わが国では罹患率において30年間で5倍に増加し，死亡率も増加傾向である．女性の癌において，罹患率1位，死亡率5位である（2009年）．他臓器癌と比較し，若年で発症することが特徴で，罹患の好発年齢は40歳代後半，死亡年齢は60歳代前半が最も多い．男性にも乳癌は発生し，罹患の男女比率はおおよそ1：100といわれている．
臨床症状
　乳房のしこりを主訴に受診することが最も多く，そのほかに乳房の痛み，乳頭からの異常分泌やびらんなどの症状が受診の契機となる．乳房の痛みと乳癌の存在は必ずしも関連しない．進行した乳癌では，腫瘤上の皮膚の陥没，浮腫，発赤，潰瘍形成などがみられることがある．腋窩のリンパ節腫脹のみや，乳房に腫瘤は触知しないが画像検査でのみ病変が指摘できる場合もある．
診断
　視触診，マンモグラフィ検査（図12-19-1），乳房超音波検査（図12-19-2A），乳房MRI検査などで乳房内病変の存在診断を行う．確定診断には病理学的検査が必要であり，穿刺吸引細胞診，分泌物細胞診，針生検，吸引式乳房組織生検などを実施する．マンモグラフィのみで同定できる微細石灰化病変の場合も，マンモグラフィガイド下で生検を実施することで確定診断が可能である．遠隔転移検索として，CT検査や骨シンチグラフィ検査，FDG-PET検査などが実施される．乳癌で増加する血液中腫瘍マーカーには，CEA，CA15-3などがある．遠隔転移を伴うような進行癌以外で診断時に増加することはまれである．
　分子生物学的な診断として，乳癌組織のエストロゲン受容体（ER），プロゲステロン受容体（progesterone receptor：PgR）の発現の有無により，ホルモン受容体陽性・陰性乳癌に分類する．また，ヒト上皮増殖因子受容体2型（human epidermal growth factor receptor type2：HER2）の有無によりHER2陽性・陰性乳癌に分類する．
鑑別診断
　表12-19-1にある乳腺の腫瘍性病変が鑑別診断となる．乳管内乳頭腫，線維腺腫，正常乳管の局所的な増殖性変化である乳腺症などが鑑別診断の対象となる．このほか，腫瘤の増大傾向の強い病変として葉状腫瘍（良性・悪性），肉腫（悪性）も念頭におく．
治療・予防
　手術療法，放射線療法，薬物療法などを組み合わせて治療を行う．手術療法は乳房と腋窩の手術からなり，原発巣の大きさや広がりから乳房部分切除術，もしくは乳房切除術を行う．腋窩に対しては，リンパ節への転移状況からセンチネルリンパ節生検，腋窩郭清術などを実施する．乳房部分切除術では残存乳房に対し，高度リンパ節転移例では胸壁，領域リンパ節に対する放射線治療を行う．
　全身薬物療法としては，化学療法（アントラサイクリン，タキサン系製剤など），ホルモン療法，分子標的療法が行われる．ホルモン受容体陽性乳癌にはタモキシフェンやアロマターゼ阻害薬などのホルモン療法の効果が期待できる．これらのホルモン療法薬は治療効果のみではなく，新規の乳癌発生を予防する効果ももつ．HER2陽性乳癌にはトラスツズマブ，ラパチニブなどの抗HER2療法薬が分子標的療法として選択される．　遠隔転移巣（骨，軟部組織，肺，肝，脳など）に対しては薬物療法が中心だが，病状により放射線治療も行う．
予後
　全国がん（成人病）センター協議会加盟施設における1997～2000年診断例の5年相対生存率は，Ⅰ期 98.2％，Ⅱ期 91.5％，Ⅲ期 67.8％，Ⅳ期 31.5％で全体では87.3％であった．［佐治重衡・戸井雅和］
■文献
京都大学大学院医学研究科外科学講座編：外科研修マニュアル，第2版，pp327-347，南江堂，東京，2009.
日本乳癌学会編：乳腺腫瘍学，pp11-68，金原出版，東京，2012.
日本乳癌学会編：乳癌取り扱い規約臨床・病理第17版，pp22-34，金原出版，東京，2012.

表12-19-1
乳腺でみられる腫瘍性病変（京都大学大学院医学研究科外科学講座，2009）">

表12-19-1

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