Breast Cancer

乳腺癌

Treatment

治疗

Hormone therapy includes tamoxifen and aromatase inhibitors. Tamoxifen competitively binds estrogen receptors. Aromatase inhibitors (anastrozole, exemestane, letrozole) block peripheral production of estrogen in postmenopausal women. Benefit of hormone therapy is greatest when tumors have estrogen and progesterone receptors, nearly as good when they have only estrogen receptors, minimal when they have only progesterone receptors, and absent when they have neither receptor. In patients with ER+ tumors, particularly low-risk tumors, hormone therapy may be used instead of chemotherapy. Aromatase inhibitors have recently been proven more effective than tamoxifen and are becoming the preferred treatment for early-stage breast cancer in receptor-positive postmenopausal patients. Adjuvant tamoxifen for 5 yr reduces annual odds of death by about 25% in premenopausal and postmenopausal women regardless of axillary lymph node involvement; treatment for 2 yr is not as effective, but treatment for > 5 yr has no advantage and may increase the likelihood that any recurrent cancer is tamoxifen-resistant. Letrozole may be used for postmenopausal women who have completed 5 yr of daily tamoxifen.

激素治疗包括三苯氧胺和芳香酶抑制剂。三苯氧胺与雌激素受体结合力。芳香酶抑制剂（阿那曲唑、依西美坦、来曲唑)阻断绝经后妇女周围雌激素的产生。当肿瘤含有雌激素和黄体激素受体时，激素治疗的益处最大，肿瘤只含有雌激素受体时疗效也差不多，只含黄体激素时疗效最差，两种受体都不存在时就没有疗效。ER＋肿瘤病人，特别是低危险肿瘤病人，激素治疗可用于替代化疗。最近证明，芳香酶抑制剂比三苯氧胺更有效，它已成为受体阳性绝经后妇女早期乳腺癌治疗的首选药物。辅助性三苯氧胺治疗5年可使绝经前和绝经后妇女死亡率减少25%左右，不管有无淋巴结受累。治疗2年的效果就没这么好，但治疗> 5年则无益，且会增加复发癌对三苯氧胺产生抗药性的可能。来曲唑可用于连续5年、每天服用三苯氧胺的绝经后妇女。

Tamoxifen can induce or exacerbate menopausal symptoms but reduces incidence of contralateral breast cancer and lowers serum cholesterol. Tamoxifen improves bone density in postmenopausal women, and there is some evidence of fracture reduction. Tamoxifen may reduce cardiovascular mortality risk. However, it significantly increases risk of developing endometrial cancer; reported incidence is 1% in postmenopausal women after 5 yr of use. Thus, if such women have spotting or bleeding, they must be evaluated for endometrial cancer. Nonetheless, the improved survival for women with breast cancer far outweighs increased risk of death due to endometrial cancer. Unlike tamoxifen, aromatase inhibitors do not cause menopausal symptoms, but they may increase risk of osteoporosis.

三苯氧胺会诱发或加重绝经期症状，但可减少对侧乳腺癌的发生率，降低血清胆固醇。三苯氧胺改善绝经后妇女的骨密度，并可减少骨折的发生。三苯氧胺可以减少心血管病死亡危险，但也会大幅增加子宫内膜癌的危险。根据报道，绝经期妇女服用5年后的发病率为1%。因此，一旦这些妇女出现斑点或出血，就必须作子宫内膜癌危险检查。然而，与内膜癌死亡危险增加相比，乳腺癌妇女处长寿命的好处更大。与三苯氧胺不同的是，芳香抑制剂不会引起绝经期症状，但可增加骨质疏松症危险。

Metastatic disease: Any indication of metastases should prompt immediate evaluation. Treatment of metastases increases median survival by only 3 to 6 mo, although relatively toxic therapies (eg, chemotherapy) may palliate symptoms and improve quality of life; the decision to undergo treatment is highly personal.医学 全在.线提供www.med126.com

转移性疾病：任何转移症状都应立即进行评估。转移治疗可使平均生存期增加3－6个月，尽管一些相对毒性的疗法（如化疗)也可以减轻症状改善生活质量。是否进行这种治疗完全取决于个人。医.学.全.在.线.网.站.提供

Choice of therapy depends on the hormone-receptor status of the tumor, length of the disease-free interval (from diagnosis to manifestation of metastases), number of metastatic sites and organs affected, and patient's menopausal status. Most patients with symptomatic metastatic disease are treated with systemic hormone therapy or chemotherapy. Radiation therapy alone may be used to treat isolated, symptomatic bone lesions or local skin recurrences not amenable to surgical resection. Radiation therapy is the most effective treatment for brain metastases, occasionally achieving long-term control. Patients with multiple metastatic sites outside the CNS should initially be given systemic therapy. There is no proof that treatment of asymptomatic metastases substantially increases survival, and it may reduce quality of life.

选择何种疗法取决于肿瘤的激素受体状况、无病间隔期（从诊断到转移出现)长短、转移部位及器官的数量和病人的绝经期状况。大多数有全身转移性疾病的病人用全身性激素治疗或化疗。对单个、有症状骨损或经不起外科手术的局部皮肤复发单独放疗即可。放射治疗对脑转移最有效，有时可获得长期控制效果。中枢神经系统以外有多处转移的病人开始时应作全身治疗。没有证据表明无症状转移疾病治疗能实质性增加生存期，它可能会降低生活质量。

Hormone therapy is preferred over chemotherapy for patients with ER+ tumors, a disease-free interval of > 2 yr, or disease that is not life threatening. Tamoxifen is often used first in premenopausal women. Ovarian ablation by surgery, radiation therapy, or use of a luteinizing-releasing hormone agonist (eg, buserelin, goserelin, leuprolide) is a reasonable alternative. Some experts combine ovarian ablation with tamoxifen therapy. If the cancer initially responds to hormone therapy but progresses months or years later, additional forms of hormone therapy may be used sequentially until no further response is seen. Aromatase inhibitors are being increasingly used as primary hormone therapy in postmenopausal women.

对ER＋肿瘤病人，无病间隔期＞2年或疾病不威胁病人生命的，可采用激素治疗而非化疗。绝经前妇女常先用三苯氧胺，也可考虑采用卵巢手术切除、放疗、或使用黄体生成素释放激素促效剂（如布舍瑞林、戈舍瑞林、醋酸亮丙瑞林)等疗法。一些专家将卵巢切除与三苯氨胺治疗相结合。如果癌症开始时激素治疗有效，几个月或几年后疾病继续发展的，就应采用别的激素治疗，直到不再看到进一步的反应。芳香酶抑制剂正越来越多地用于绝经后妇女的一线激素治疗。

The most effective cytotoxic drugs for treatment of metastatic breast cancer are capecitabine, doxorubicin, gemcitabine, the taxanes paclitaxel and docetaxel, and vinorelbine. Response rate to a combination of drugs is higher than that to a single drug, but survival is not improved and toxicity is increased. Thus, some oncologists use single drugs sequentially.

治疗转移性乳腺癌的最有效细胞毒类药有卡培他滨、阿霉素、二氟脱氧胞嘧啶、紫杉烷类（紫杉醇和紫杉萜［泰素帝］)、长春瑞滨等。组合药物的有效率大于单一药物，但生存期并没有延长，且毒性增加。因此，一些肿瘤医师倾向连续使用单一药物。

For tumors with amplification of HER2/neu, the humanized monoclonal antibody trastuzumab is effective in treating and controlling visceral metastatic sites. It is used alone or with hormone therapy or chemotherapy.

对HER2/neu放大肿瘤，人体单克隆抗体曲妥单抗在治疗和控制内脏转移时有效，它既可单独使用，也可与激素治疗或化疗合用。

About 10% of patients with bone metastases eventually develop hypercalcemia, which can be treated with IV bisphosphonates (eg, pamidronate).

10%的骨转移病人最终会患高钙血症，它可以用二膦酸盐静脉治疗（如氨羟二磷酸二钠)。