不能手术的局部晚期乳腺癌NCCN指南2015v3

Inoperable Locally Advanced Breast Cancer

不能手术的局部晚期乳腺癌

(Clinical stage IIIA [except for T3, N1, M0], clinical stage IIIB, or clinical stage IIIC)

(临床分期ⅢA[除T3N1M0外]、ⅢB或ⅢC)

For patients with inoperable, non-inflammatory, locally advanced disease at presentation, the initial use of anthracycline-based preoperative systemic therapy with or without a taxane is standard therapy. Patients with locally advanced breast cancer that is HER2-positive should receive an initial chemotherapy program that incorporates preoperative trastuzumab and possibly pertuzumab. Local therapy following a clinical response to preoperative systemic therapy usually consists of: 1) total mastectomy with level I/II ALN dissection, with or without delayed breast reconstruction; or 2) lumpectomy and level I/II axillary dissection.山东省肿瘤医院呼吸肿瘤内科张品良

对于在发病时不能手术、非炎性、局部晚期患者，最初使用以蒽环类为基础的术前系统治疗±紫杉烷是标准治疗。HER2阳性的局部晚期乳腺癌患者应该接受术前联合曲妥珠单抗和可能的帕妥珠单抗初始化疗方案。在对术前系统治疗获得临床应答之后的局部治疗一般包括：1)全乳切除术联合Ⅰ/Ⅱ级ALN清扫±延时乳房再造；或2)乳房局部病灶切除术与Ⅰ/Ⅱ级腋窝淋巴结清扫。

Both local treatment groups are considered to have sufficient risk of local recurrence to warrant the use of chest wall (or breast) and supraclavicular node irradiation. If internal mammary lymph nodes are involved, they should also be irradiated. Without detected internal mammary node involvement, consideration may be given to include the internal mammary lymph nodes in the radiation field (category 2B). Adjuvant therapy may involve completion of planned chemotherapy regimen course if not completed preoperatively, followed by endocrine therapy in patients with hormone receptor-positive disease. Up to one year of total trastuzumab therapy should be completed if the tumor is HER2-positive (category 1). Endocrine therapy and trastuzumab can be administered concurrently with radiation therapy if indicated.

两个局部治疗组都被认为局部复发风险足以有理由使用胸壁(或乳腺)以及锁骨上淋巴结照射。如果内乳淋巴结被累及，也应该照射。未检出内乳淋巴结受累，可考虑放射野包括内乳淋巴结(2B类)。如果术前未完成辅助治疗可包括完成计划的化疗疗程，在激素受体阳性的患者中序贯内分泌治疗。如果肿瘤HER2阳性应该完成最长一年的全部曲妥珠单抗治疗(1类)。如果有指征内分泌治疗和曲妥珠单抗可以与放疗同时给予。

Patients with an inoperable stage III tumor with disease progression during preoperative systemic therapy should be considered for palliative breast irradiation in an attempt to enhance local control. In all subsets of patients, further systemic adjuvant chemotherapy after local therapy is felt to be standard.

Tamoxifen (or an aromatase inhibitor if postmenopausal) should be added for those with hormone receptor-positive tumors, and trastuzumab should be given to those with HER2-positive tumors. Post-treatment follow-up for women with stage III disease is the same as for women with early-stage invasive breast cancer.

在术前系统治疗期间疾病进展的不能手术的Ⅲ期肿瘤患者应该考虑姑息性乳腺照射以求增加局部控制。在所有患者亚群中，在局部治疗后进一步系统的辅助化疗认为是规范的。对于那些激素受体阳性的肿瘤患者应该加上他莫昔芬(或一种芳香化酶抑制剂如果是绝经后)，而对于那些HER2阳性的肿瘤患者应该给予曲妥珠单抗。对于Ⅲ期疾病女性的治疗后随访和早期浸润性乳腺癌女性一样。

Post-Therapy Surveillance and Follow-up

治疗后监测与随访

Post-therapy follow-up is optimally performed by members of the treatment team and includes the performance of regular history/physical examinations every 4 to 6 months for the first 5 years after primary therapy and annually thereafter. Mammography should be performed annually.

由治疗组成员实施治疗后随访是最理想的，定期病史/体检初次治疗后最初5年每4-6个月尔后每年1次。乳腺摄影应该每年1次。

The routine performance of alkaline phosphatase and liver function tests are not included in the guidelines. In addition, the panel notes no evidence to support the use of “tumor markers” for breast cancer, and routine bone scans, CT scans, MRI scans, PET scans, or ultrasound examinations in the asymptomatic patient provide no advantage in survival or ability to palliate recurrent disease and are, therefore, not recommended.

常规碱性磷酸酶和肝功能检查未收入该指南中。另外，小组指出没有证据支持乳腺癌使用“肿瘤标志物”，而常规骨扫描、CT扫描、MRI扫描、PET扫描或超声检查在无症状患者中没有提供生存优势或减轻复发疾患的性能，因此未被推荐。

The use of dedicated breast MRI may be considered as an option for post-therapy surveillance and follow-up in women at high risk for bilateral disease, such as carriers of BRCA1/2 mutations. Rates of contralateral breast cancer following either breast-conserving therapy or mastectomy have been reported to be increased in women with BRCA1/2 mutations when compared with patients with sporadic breast cancer. (See NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian and NCCN Guidelines for Breast Cancer Screening and Diagnosis).

使用乳腺专用的MRI可以考虑作为高危双侧疾病如BRCA1/2突变携带者女性治疗后监测与随访的一个选择。已报道在保乳治疗或乳腺切除术后对侧乳腺癌发生率与散发性乳腺癌患者相比在BRCA1/2突变女性中增加。(见遗传性/家族性高危评估NCCN指南：乳腺与卵巢以及乳腺癌筛查与诊断NCCN指南)。

The panel recommends that women with intact uteri who are taking adjuvant tamoxifen should have yearly gynecologic assessments and rapid evaluation of any vaginal spotting that might occur because of the risk of tamoxifen-associated endometrial carcinoma in postmenopausal women. The performance of routine endometrial biopsy or ultrasonography in the asymptomatic woman is not recommended. Neither test has demonstrated utility as a screening test in any population of women. The vast majority of women with tamoxifen-associated uterine carcinoma have early vaginal spotting.

专家组推荐具有完整子宫的女性采取辅助他莫昔芬者应该每年一次妇科评估并且在绝经后女性中凡是阴道少量出血要迅速评估因为或许存在他莫昔芬相关的子宫内膜癌风险。不推荐在无症状女性中常规实施子宫内膜活组织检查或超声检查。两项检查作为筛查在任何女性群体中都未证明有效。绝大多数与他莫昔芬相关的子宫癌女性有早期阴道出血。

If an adjuvant aromatase inhibitor is considered in women with amenorrhea following treatment, baseline levels of estradiol and gonadotropin followed by serial monitoring of these hormones should be performed if endocrine therapy with an aromatase inhibitor is initiated.

在月经不调女性中后续治疗如果考虑一种辅助芳香化酶抑制剂,如果开始用一种芳香化酶抑制剂内分泌治疗应该完成基线水平的雌二醇和促性腺激素然后连续监测这些激素。

Bilateral oophorectomy assures postmenopausal status in young women with therapy-induced amenorrhea and may be considered prior to initiating therapy with an aromatase inhibitor in a young woman.

在治疗所致闭经的年轻女性中双侧卵巢切除术可确保绝经状态,并且在一个年轻女性中可在启动芳香化酶抑制剂治疗前考虑。

Symptom management for women on adjuvant endocrine therapies often requires treatment of hot flashes and the treatment of concurrent depression.

对于辅助内分泌治疗女性的症状管理通常需要治疗潮热和并发的抑郁症。

Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI) has been studied and is an effective intervention in decreasing hot flashes.

文拉法辛、5-羟色胺去甲肾上腺素再摄取抑制剂（SNRI）已进行了研究，在减轻潮热方面是一种有效干预。

There is evidence suggesting that concomitant use of tamoxifen with certain SSRIs (eg, paroxetine, fluoxetine) may decrease plasma levels of endoxifen, an active metabolite of tamoxifen.

有证据表明，他莫昔芬与SSRIs类药物（如帕罗西汀，氟西汀）同时使用可降低血浆水平去甲基他莫昔芬，他莫昔芬的活性代谢物。

These SSRIs/SNRIs may interfere with the enzymatic conversion of tamoxifen to endoxifen by inhibiting a particular isoform of CYP2D6.

这些SSRIs/SNRIs可能通过抑制CYP2D6的特定亚型干扰他莫昔芬酶转化为羟基他莫西芬。

However, the mild CYP2D6 inhibitors such as citalopram, escitalopram, sertraline, and venlafaxine appear to have no or only minimal effect on tamoxifen metabolism.

然而，温和的CYP2D6抑制剂如西酞普兰、西酞普兰、舍曲林与文拉法辛似乎对他莫昔芬代谢没有或只有极小的影响。

Follow-up also includes assessment of patient adherence to ongoing medication regimens such as endocrine therapies.

随访还包括评估患者坚持正在进行的药物治疗方案如内分泌治疗情况。

Predictors of poor adherence to medication include the presence of side effects associated with the medication, and incomplete understanding by the patient of the benefits associated with regular administration of the medication.

药物坚持不良的预测因子，包括存在药物相关的副作用和患者对规律用药获益的不完全理解。

The panel recommends the implementation of simple strategies to enhance patient adherence to endocrine therapy, such as direct questioning of the patient during office visits, as well as brief, clear explanations on the value of taking the medication regularly and the therapeutic importance of longer durations of endocrine therapy.

小组建议实施简单的策略，以提高患者坚持内分泌治疗，如在办公室拜访期间直接询问病人，以及简短、明确的解释，规律服用药物的价值和长期内分泌治疗的重要性。

Lymphedema is a common complication after treatment for breast cancer.

淋巴水肿是乳腺癌术后常见的并发症。

Factors associated with increased risk of lymphedema include extent of axillary surgery, axillary radiation, infection, and patient obesity.

与淋巴水肿的风险增加相关的因素包括腋窝手术，腋窝的辐射程度，感染，患肥胖。

The panel recommends educating the patients on lymphedema, monitoring for lymphedema, and referring for lymphedema management as needed.

小组建议教育患者有关淋巴水肿、淋巴水肿监测并根据需要在淋巴水肿管理。

Evidence suggests that a healthy lifestyle may lead to better breast cancer outcomes.

有证据表明，健康的生活方式可能会导致更好的乳腺癌的结果。

A nested case control study of 369 women with ER-positive tumors who developed a second primary breast cancer compared with 734 matched control patients who did not develop a second primary tumor showed an association between obesity (body mass index [BMI]≥30), smoking, and alcohol consumption and contralateral breast cancer.

一项巢式病例对照研究比较了369例发生第二原发乳腺癌ER阳性女性与734例相匹配的未发生第二原发肿瘤的对照组患者显示在肥胖（体重指数[BMI]≥30）、吸烟、饮酒与对侧乳腺癌之间相关。

A prospective study of 1490 women diagnosed with stage I-III breast cancer showed an association between high fruit and vegetable consumption, physical activity, and improved survivorship, regardless of obesity.

对1490例Ⅰ- Ⅲ期乳腺癌女性的一项前瞻性研究表明，在水果和蔬菜摄入量、体力活动高之间相关，不管肥胖与否，均改善生存。

There is emerging evidence that obesity is associated with poorer outcomes for certain subtypes of breast cancers.

新的证据表明，肥胖与某些亚型乳腺癌预后较差相关。

The study by the Women’s Intervention Nutrition group randomized early-stage breast cancer patients to an intervention group and a control group.

女性营养干预研究将早期乳腺癌患者随机分入干预组和对照组。

The intervention consisted of eight one-on-one visits with a registered dietitian who had been trained on a low-fat eating plan.

干预措施包括八次一对一的访问已经接受低脂肪饮食计划培训的注册营养师。

OS analysis showed no significant difference between the two study arms (17% for the intervention vs. 13.6% without); however, subgroup analysis showed that those with ER- and PR-negative disease who were part of the intervention group saw a 54% improvement in OS.

总生存分析显示，2个研究组之间没有显着性差异（17%的干预比13.6%）；然而，亚组分析表明，那些干预组的ER和PR阴性患者，OS提高了54%。

The NCCN Panel recommends an active lifestyle and ideal body weight (BMI 20-25) for optimal overall health and breast cancer outcomes.

NCCN专家组推荐一种积极的生活方式和理想体重（BMI 20-25）对于最佳的整体健康和乳腺癌预后。

Many young women treated for breast cancer maintain or regain premenopausal status following treatment for breast cancer.

许多治疗的年轻乳腺癌女性在乳腺癌治疗后维持或恢复绝经前状态。

For these women, the NCCN Panel discourages the use of hormonal birth control methods, regardless of the hormone receptor status of the tumor.

对于这些妇女，NCCN小组不鼓励应用激素节育方法，这与肿瘤的激素受体状态无关。

Alternative birth control methods are recommended, including intrauterine devices, barrier methods, and, for those with no intent of future pregnancy, tubal ligation or vasectomy for the partner.

建议选择的避孕方法，包括宫内节育器、屏障避孕法，以及，对那些没有怀孕意图者，输卵管结扎术或伴侣输精管结扎术。

Breastfeeding during endocrine or chemotherapy treatment is not recommended by the NCCN Panel because of risks to the infant.

内分泌治疗或化疗期间母乳喂养是不是由NCCN小组建议由于对婴儿的风险。

Breastfeeding after breast-conserving treatment for breast cancer is not contraindicated.

哺乳后乳腺癌保乳治疗的乳腺癌患者是没有禁忌。

However, lactation from an irradiated breast may not be possible, or may occur only with a diminished capacity.

然而，照射的乳房哺乳或许是不可能的，或可能只发生与减少能力。

The panel recommends that women on an adjuvant aromatase inhibitor or who experience ovarian failure secondary to treatment should have monitoring of bone health with a bone mineral density determination at baseline and periodically thereafter.

专家小组建议，对辅助性芳香抑制剂或治疗引起的继发性卵巢功能衰竭的女性应在基线和此后定期测定骨矿物密度监测骨健康。

The use of estrogen, progesterone, or selective ER modulators to treat osteoporosis or osteopenia in women with breast cancer is discouraged.

在乳腺癌女性中使用雌激素、黄体酮或者选择性雌激素受体调节剂治疗骨质疏松症或骨量减少令人沮丧。

The use of a bisphosphonate is generally the preferred intervention to improve bone mineral density.

一通常是首选的干预为了提高骨矿物质密度使用双膦酸盐。

Recent data show that adjuvant denosumab significantly reduces fractures in postmenopausal women receiving adjuvant therapy aromatase inhibitors, and improves bone mineral density.

最新数据显示在接受芳香化酶抑制剂辅助治疗的绝经后女性中辅药地诺单抗显著降低骨折，和提高骨矿物质密度。

Optimal duration of bisphosphonate therapy has not been established.

尚未确定双膦酸盐治疗的最佳持续时间。

Factors to consider for duration of anti-osteoporosis therapy include bone mineral density, response to therapy, and risk factors for continued bone loss or fracture.

事实或者的考虑为抗骨质疏松治疗的持续时间包括骨矿物质密度，治疗应答，和危险因素为持续的骨丢失或者骨折。

Women treated with a bisphosphonate should undergo a dental examination with preventive dentistry prior to the initiation of therapy, and should take supplemental calcium and vitamin D.

接受双磷酸盐治疗的女性应该在治疗开始之前接受预防性牙科检查，并应该补充钙和维生素D。