淋巴结阴性乳腺癌患者辅助治疗的研究进展

淋巴结阴性乳腺癌患者中有20%～30%经手术治疗后复发和转移.本文综述了如何选择需要内分泌治疗和/或化疗的淋巴结阴性乳腺癌患者,以及如何选择正确的治疗模式.     

早期乳腺癌保乳术后的放疗时机

早期乳腺癌保留乳房手术加放疗的疗效与根治术相同。对术后放疗时机的问题有一些回顾性和随机性研究,但无明确结论,近期的一些随机研究尚需要长期随访。总的来说,对于无需术后化疗的病人应尽早放疗,建议手术放疗间隔最好不超过8周。术后放疗、化疗顺序对疗效无显著影响,先放疗或先化疗均可以。对于腋窝淋巴结转移数较多的远地转移高危病人,术后可先做辅助化疗,但放疗不应延迟到术后7个月以后。如果手术切缘阳性,放疗应尽早开始。同步放化疗可以在不延迟放化疗的基础上提高局部疗效,但疗效提高有限,同时会增加急性和晚期毒副作用,不宜作为常规治疗。特殊病人需要使用时,应选择有效低毒的化疗方案,以降低治疗带来的急性毒副作用和晚期并发症。缩短放疗总时间对需要化疗的病人可以缩短手术到化疗的时间间隔,目前可行的方式有大分割放疗和乳腺瘤床同步补量技术。缩短放疗总时间是否能对疗效改善有影响,有待于临床资料证实。     

Timing of adjuvant systemic therapy and radiotherapy after breast-conserving surgery and mastectomy

In the last two decades, systemic adjuvant treatment for breast cancer, in association with radiotherapy, has been shown to prolong disease-free survival and overall survival in patients with operable breast tumors. So far, the optimal sequence of systemic therapy and radiotherapy for breast cancer patients after conservative surgery or mastectomy is unclear. Several retrospective analyses showed a possible detrimental effect on local regional recurrence rates when radiation therapy is delayed after chemotherapy. On the other hand, delaying chemotherapy after radiotherapy may increase the risk of distant failure and affect the survival. Concurrent administration of targeted treatment (e.g. non-anthracycline/taxane containing chemotherapy, trastuzumab, endocrine therapy) with radiotherapy is considered a valid option. A “tailored” approach on sequencing of chemotherapy and radiotherapy which takes into account various variables, such as histological and biological features of the tumor, as well as the patient status and the treatment modality is required in order to optimize the delivery of adjuvant treatments. This review focuses on the effects of timing of chemotherapy–radiotherapy and risks of relapse, in terms of locoregional and distant recurrence in patients with operable breast cancer.     

Tattoo allergy in patients receiving adjuvant radiotherapy for breast cancer

Tattooing is routinely employed prior to radiotherapy treatment but allergies to tattoos are rare. New information on the incidence of tattoo allergy at St George Hospital is presented with details of two clinical cases. The literature on tattoo allergy has been unable to estimate the incidence of allergic reaction to tattoos because the total number of patients treated is unknown and not all patients were followed up. Our radiation oncology population for the first time has provided a known denominator, but wide confidence intervals prevent an accurate estimate of the incidence. Salient issues about tattoo allergy are highlighted based on a review of the published literature from 1966 to 1998.     

保乳手术在乳腺癌治疗中的应用

目的 :研究保乳手术在Ⅰ、Ⅱ期乳腺癌中的治疗效果。方法 :从 1990年 3月到 2 0 0 4年 3月 ,对直径≤3cm ,肿瘤边缘距乳晕≥ 2cm的部分患者施行保乳手术 ,部分肿瘤直径 >3cm的患者先行术前化疗 ,肿瘤缩小后再做保乳手术。手术切除肿瘤周围约 2cm的正常组织 ,达到切缘阴性 ,腋窝清扫范围为Ⅰ、Ⅱ水平淋巴结。开始时应用 1切口设计 ,后来改为 2切口。术后先进行放疗 ,再进行化疗和 (或 )内分泌治疗。结果 :2 6 5例保乳手术腋窝淋巴结清扫数目为 5～ 2 9个 ,平均 16个。本组患者局部复发部位均为乳腺 ,无腋窝复发者 ,三年、五年、十年生存率分别为 99%、94 %、80 % ,局部复发率为 5 .4 %、7%、7.7% ,乳房保留率为 97.8%、93%、88% ,保留乳房的美容效果满意率为 83.2 %。结论 :保乳手术适用于Ⅰ、Ⅱ期乳腺癌患者 ,可以取得良好的生存率、局部控制率和美容效果 ,是乳腺癌治疗的首选术式。     

Prognostic role of adjuvant radiotherapy in triple‐negative breast cancer: A historical cohort study

The value of adjuvant radiotherapy in triple‐negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N = 1,138) were included. Survival between patients receiving mastectomy only, breast‐conserving therapy (BCT, lumpectomy and adjuvant radiotherapy) and mastectomy with radiotherapy were compared, and adjusted for demography, tumor characteristics and chemotherapy types. Median age at diagnosis was 53 years (range: 23–96 years). Median tumor size at diagnosis was 2.5 cm and most patients had lymph node‐negative disease. The majority of patients received adjuvant chemotherapy (n = 861, 76%) comprising predominantly anthracycline‐based regimes. In 775 women with T1‐2, N0‐1, M0 TNBCs, 5‐year relative survival ratio (RSR) was highest in patients undergoing mastectomy only (94.7%, 95% CI: 88.8–98.8%), followed by BCT (90.8%, 95% CI: 85.0–94.7%), and mastectomy with radiotherapy (82.3%, 95% CI: 73.4–88.1%). The adjusted risks of mortality between the three groups were not significantly different. In 363 patients with T3‐4, N2‐3, M0 TNBCs, BCT was associated with highest 5‐year RSR (94.1%, 95% CI: 81.3–99.4%), followed by mastectomy with radiotherapy (62.7%, 95% CI: 54.3–70.1%), and mastectomy only (58.6%, 95% CI: 43.5–71.6%). Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy appears to be independently associated with a survival gain in locally advanced as well as in very young TNBC.     

Prognostic significance of biologic markers in node-negative breast cancer patients: a prospective study

It is generally thought that future advances in the treatment and cure of breast cancer patients will be made possible through a deeper understanding of tumor biology and an improved capability to define the prognosis of each single patient. This will lead to the formulation of new, more selective, and patient-tailored therapies. It is therefore important, when studying potential prognostic factors, to follow methodologic requirements and guidelines which involve the carrying out of prospective studies as confirmatory steps. Repeatedly or recently investigated prognostic markers (tumor size, menopausal status, ER, PgR, ³H thymidine labeling index, c-erbB-2 and p27 expression) were evaluated on a series of 286 prospectively recruited node negative breast cancer patients who underwent loco-regional treatment alone and were closely followed. The individual and relative prognostic contribution of each variable with respect to other factors, as well as their ability to identify node negative patients at risk, were assessed by univariate and multivariate analysis. At a five-year follow-up, only tumor size (p=0.021) and TLI (p=0.016) individually proved to be significant prognostic indicators of relapse-free survival. Conversely, p27 expression was not related to RFS and c-erbB-2 expression appeared to have only a short-term effect on patient prognosis. TLI and tumor size, tested in multivariate analysis along with ER and menopausal status, maintained their independent prognostic relevance. The study, performed on a large series of node-negative patients given loco-regional treatment alone, for the first time prospectively recruited, showed the prognostic relevance of TLI and its independence from other clinico-pathologic and biologic factors over a five-year period.     

Dietary intervention as adjuvant therapy in breast cancer patients — a feasibility study

Summary To evaluate the feasibility of using a low-fat diet (i.e. 20–25% of energy (E%) as fat) as a component of adjuvant therapy for breast cancer patients, 240 females aged 50–65 years and operated for a stage I-II breast cancer were entered into a randomized study. The intervention group (n = 121) was to reduce dietary fat intake to 20–25 E% and to increase the intake of carbohydrates. Dietary counselling complemented other adjuvant treatments and the patients were followed for two years. No dietary advice was given to patients in the control group (n = 119).There was no significant difference between the groups in terms of base-line nutrient intake except for higher energy intake in the control group (p < 0.05). Only 52% of the patients in the intervention group followed through with the dietary regimen for two years, and 89% of the patients in the control group had a two-year follow-up. Energy intake decreased in both groups after two years, and the difference between the two groups remained (p < 0.01). Total fat intake decreased from 36.2 E% to 22.2 E% after one year in the intervention group and remained at that level after two years. Total fat intake in the control group decreased by 3.6 E% after two years.The low compliance raises concern about the protocol design. The study nevertheless indicates that a long-term reduction of dietary fat intake can be implemented in breast cancer patients.     

Feasibility of concurrent adjuvant chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer

BACKGROUND: The optimal sequence of chemotherapy (CT) and radiotherapy (RT) remains uncertain after breast-conserving surgery (BCS). The current study was performed to evaluate whether the concurrent RT with CT increases the toxicities. METHODS: Two hundred and thirty-eight patients with stages I and II breast cancers were prospectively allocated to concurrent CT and RT (n = 133) and sequential CT and RT (n = 105) after BCS. In the sequential group, RT was started after the completion of three cycles of CT and additional three cycles of CT were delivered after RT. RESULTS: There was no significant difference in Grade 3 or 4 hematologic toxicities during CT between the two groups. Radiation related adverse effects were not different between the two groups. During the median follow-up period of 42 months (range: 16-60 months), 18 patients (13.5%) of the concurrent group had systemic recurrence of breast cancer, whereas 20 patients (19.1%) of the sequential group had systemic recurrence. Disease-free survival and local recurrence were not different between the two groups. CONCLUSIONS: Concurrent CT and RT were not associated with increased toxicity and showed reasonable cosmetic results. The current study indicates that concurrent RT and CT after BCS is a feasible treatment modality with an advantage of shortening the treatment time.     

放射治疗在早期乳腺癌保乳术中的价值

目的：进一步证实放射治疗在早期乳腺癌保乳术中的重要性。方法：1994年12月～2001年12月本院共收治237例早期乳腺癌。其中83例做保乳手术。154例做改良根治术。保乳术后全部患者接受放疗。放疗的范围根据肿块的大小、部位、腋淋巴结是否受累而定。胸壁切线剂量予8MV—X线5000cGy。肿瘤瘤床加电子线1500cGy。改良根治术后仅3例作放疗。结果：保乳组和改良组局部复发各1人。保乳组区域淋巴结复发1例。改良组无区域淋巴结复发，有肝转移、肺转移各1人。两组各死亡1人。保乳组五年生存率96．49％，改良组98．61％。保乳组双侧乳房外形基本一致，柔软，有弹性。结论：早期乳腺癌保乳术加放射治疗，效果与改良根治术相似，并伴良好美容效果。     

大分割放疗治疗早期乳腺癌保乳手术后患者的疗效及安全性

目的分析两种放疗方案治疗早期乳腺癌保乳手术后患者的近期应用效果及安全性。方法将110例行保乳手术的早期乳腺癌患者依据保乳术后采用的放疗方法不同分为观察组(采用大分割放疗,n=55)与对照组(采用常规分割放疗,n=55),治疗后随访2年,比较两组生存情况、危及器官所受剂量、急慢性不良反应发生率、美容效果、治疗次数与治疗费用。结果两组患者近期生存率均达100%。观察组患者危及器官肺、心脏、脊髓、肝脏所受放疗剂量均明显低于对照组(P<0.01)。两组患者急慢性不良反应以Ⅰ级及Ⅱ级为主,且两组急慢性不良反应发生率比较,差异均无统计学意义(P>0.05)。两组患者美容效果比较,差异无统计学意义(P>0.05)。观察组患者治疗次数、治疗费用均少于对照组(P<0.01)。结论与常规分割放疗方案相比,大分割放疗有助于提高早期乳腺癌保乳术后患者疗效,有更好的社会经济学效益,且能减少危及器官受量,安全性可靠,美容效果相当。     

Cost-effectiveness of new guidelines for adjuvant systemic therapy for patients with primary breast cancer.

BACKGROUND: In this study, the potential impact of a new national guideline for adjuvant systemic therapy in breast cancer (introduced in The Netherlands in 1998) was assessed, as well as the modifications of this guideline, issued in 2001. Both the change in total number of patients eligible for adjuvant therapy, as well as the cost-effectiveness of the changed clinical management of these patients were analysed. PATIENTS AND METHODS: Percentages of patients who would be eligible for adjuvant therapy in 1994, 1998 and 2001 were estimated, based on clinical data from 127 patients, who were operated on in 1994. Ten-year overall survival rates were used as a measure of effectiveness, based on the two most recent EBCTCG meta-analyses. Actual resource costs were calculated. With a decision analytic model, the incremental cost-effectiveness ratios (1998 versus 1994, and 2001 versus 1998) were calculated. RESULTS: The introduction of the 1998 guideline resulted in a relative increase of 80% in the total number of patients eligible for adjuvant therapy, compared with 1994 (from 40% to 72% of all patients with primary breast cancer). With an estimated absolute increase of 10-year overall survival of 2%, the 1998 guideline was found to have an expected incremental cost-effectiveness ratio of about 4837 per life-year gained. CONCLUSIONS: Introduction of the new guideline considerably affected the number of patients eligible for adjuvant systemic therapy for breast cancer. The associated incremental cost-effectiveness ratio is well within the range of values that are generally considered acceptable.     

Risk factors and specific cancer types of second primary malignancies in patients with breast cancer receiving adjuvant radiotherapy: a case-control cohort study based on the SEER database

Patients with breast cancer can survive and live a long, cancer-free life; however, late complications of treatment, such as second primary malignancies (SPMs), have emerged as a competing cause of death and morbidity. We conducted a long-term population-based cohort study to identify the risk factors for SPMs and specific secondary cancer types after various latency periods of irradiated breast cancer. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) for independent risk factors for SPM. We also calculated the HR of each specific cancer type and the latency time to specific SPMs. The risk of SPM was statistically significantly higher in patients with adjuvant RT than in patients without adjuvant RT (adjusted HR [aHR]: 1.105, 95% CI: 1.013-1.206). Compared with the control group, the case group had significantly increased risks of contralateral breast cancer (aHR: 1.268, 95% CI: 1.112-1.445), lung cancer (aHR: 1.218, 95% CI: 1.049-1.565), and urinary system cancer (aHR: 1.702, 95% CI: 1.140-2.543). Adjuvant RT for breast cancer increases the risk of SPM. Contralateral breast cancer, lung cancer, and bladder cancer were significant SPMs after breast RT, although the cumulative risk of SPM was low, at approximately 6, 10, and 13 cancers per 1000 women with irradiated breasts at latency periods of 5, 10, and 15 years, respectively, after breast RT.     

Cognitive effects of hormonal therapy in early stage breast cancer patients: a prospective study

Objective: The primary purpose of this study was to evaluate the cognitive effects of adjuvant hormonal therapies in breast cancer patients. Participants and Methods: Post‐menopausal breast cancer patients scheduled to receive tamoxifen (n=31) or anastrozole (n=14) completed neuropsychological testing around the time of commencement of treatment (T1), and again 5–6 months later (T2). A sample of healthy female volunteers (n=28) was tested at comparable intervals. A standardized regression‐based approach was used to assess cognitive change. This method uses test/retest scores of the healthy control group to generate an equation that predicts T2 scores from T1 scores. The difference between the predicted and obtained T2 scores divided by the standard error of the estimate produces a deviation score that reflects the discrepancy from the T1–T2 difference scores that would be expected on the basis of practice and error alone. Results: Analysis of individual deviation scores revealed that both the patients taking tamoxifen and those taking anastrozole were more likely than healthy controls to show reliable cognitive decline from T1 to T2 (39, 64, and 7%, respectively). Processing speed and verbal memory were the cognitive domains most affected. Conclusion: These data suggest that hormonal therapies exert a subtle negative influence on cognition in breast cancer patients. Further analyses indicated that this effect was not fully accounted for by demographic factors or fatigue. Methodological limitations of the current study are addressed, along with recommendations for future studies in this area. Copyright © 2008 John Wiley & Sons, Ltd.     

Carcinoma of the male breast: A review of adjuvant therapy

The purpose of the present paper was to evaluate the characteristics and outcomes of male breast cancer patients seen for adjuvant therapy at a single institution. A retrospective review of computerized records in the Departments of Medical and Radiation Oncology at the Royal Prince Alfred Hospital (RPAH) was undertaken. Between 1983 and 1996, 24 men were referred for treatment of breast cancer. Of these, 19 had localized breast cancer, four had metastatic disease and one had ductal carcinoma in situ (DCIS). The median age was 57.5 years (range: 26–78) and median follow- up was 6.2 years (range: 0.6–36). Pathological staging was performed. Survival was assessed using actuarial life table analysis. Of the 19 patients who presented with localized disease, there were 12 T₁ , five T₂ and two T₄ cancers. Eleven patients had axillary lymph node involvement. Ten patients were oestrogen receptor (ER) positive, two patients were ER negative and seven patients had unknown receptor status. All patients underwent surgery. Eleven patients received radiotherapy. The median dose and dose per fraction were 50 Gy and 2 Gy, respectively. Adjuvant systemic therapy was delivered to 10 patients, of whom nine were node-positive. Four patients received chemotherapy alone, three patients received chemotherapy and tamoxifen, and three patients received tamoxifen only. Seven patients relapsed (one local, five distant, one both). Of the two patients with local relapses, one had received radiotherapy. Of the distant failures, four of six patients had no systemic therapy. There were only two node-positive patients who were not given systemic treatment and both relapsed. Median survival in all patients with invasive cancer was 7.5 years, and in those with localized disease it was 7.6 years. The median survival of node-positive patients was 3.8 years. In node-negative patients the median survival had not been reached at a median follow-up of 6.2 years. The majority of patients (12/14) with known receptor status were ER+, a finding that parallels those of other studies. Local control rates were 88% (7/8) in patients who had mastectomy alone and 91% (10/11) in those patients receiving adjuvant radiotherapy. Systemic therapy was found to be beneficial in patients with node-positive disease. Chemotherapy was administered more frequently than hormonal therapy. The median survivals were consistent with those reported in other series.     

Early cardiac toxicity following adjuvant radiotherapy of left-sided breast cancer with or without concurrent trastuzumab

Purpose

To evaluate the influence of concurrent trastuzumab on the cardiotoxicity in patients receiving left-sided adjuvant radiotherapy.

Materials and Methods

Medical records of stage I-III left-sided breast cancer patients, including 64 receiving concurrent trastuzumab with radiotherapy and 73 receiving radiotherapy alone were retrospectively reviewed. All of the patients had normal LVEF after adjuvant chemotherapy. Information of doses volume to cardiac structures was collected. Cardiac events were assessed according to CTC 2.0.

Results

Median follow-up of LVEF and clinical assessment of cardiac function from the initiation of radiotherapy was 6.7 months (range 3–60.9) and 26 months (range 6.4–60.9), respectively. Grade 1 LVEF dysfunction occurred in 5 (7.8%) and 3 (4.1%) patients of the concurrent-trastuzumab and radiotherapy alone cohort, respectively. Trastuzumab was the only significant factor influencing absolute LVEF decrease in univariate analysis. In multivariate analysis of concurrent-trastuzumab cohort, IMC radiotherapy and start trastuzumab during radiotherapy were independent risk factors. For concurrent cohort, mean heart dose, as well as D₁₀-D₃₀, D₅₀-D₅₅, V₅-V₂₀ of the heart and D₃₀-D₄₅, D₆₅-D₇₅, V₆-V₁₅ of the LV were significantly higher in patients developing LVEF dysfunction.

Conclusions

Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy. However, increases in mean dose and low–dose volume of cardiac structures are associated with a higher risk of acute LVEF dysfunction.     

广泛导管内成分与保乳术后局部复发风险评估

保乳手术已成为早期乳腺癌的主要治疗手段,评估其局部复发的首选指标为广泛导管内成分(EIC).许多研究证实,EIC阳性者局部复发率较高,但远期生存率并不明显低于阴性者.除了病理检查之外,钼靶X线对检出EIC也有较高的参考作用.从分子生物学角度看,EIC与染色体1q21-23区域的等位基因缺失、cerbB-2过表达等因素正相关,而与p53的过度表达、细胞凋亡没有明显关系.EIC的检测对于早期乳腺癌的综合治疗方案选择具有重要指导意义.