乳腺癌相关信号转导通路的研究进展

乳腺癌的术后辅助全身化疗总是取得不断的进展。从环磷酰胺、甲氨喋呤和氟尿嘧啶的三联ＣＭＦ方案减低患者术后复发和死亡风险开始,辅助化疗方案在不断更新,蒽环类药物以及随后的紫杉醇类药物序贯或者联合应用已经成为目前主打的辅助化疗策略。患者的机体状况、肿瘤特定的生物学表型以及药物的疗效和毒性是制定辅助化疗方案必须综合考虑的因素。传统的预后指标评估患者复发风险仍然十分重要,此外新的基因组工具（如ＯｎｃｏｔｙｐｅＤＸ和Ｍａｍｍａｐｒｉｎｔ）便于我们更有选择地为不同的患者制定个体化的术后辅助治疗。     

Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women: Results from a controlled randomised trial

BackgroundAdjuvant treatment with tamoxifen reduces the risk of contralateral breast cancer in hormone-responsive postmenopausal patients, whereas the effect in premenopausal women has not been fully elucidated. We have therefore studied the effect of tamoxifen on contralateral breast cancer in premenopausal women in a controlled randomised trial.Patients and methodsPremenopausal women (564) with stage II breast cancers were randomised to 2 years of tamoxifen versus control irrespective of oestrogen receptor (ER) and progesterone receptor (PgR) status. The median follow-up for patients not developing a contralateral cancer was 14 years.ResultsIn the control group 35 women, and in the tamoxifen group 17 women, developed a contralateral breast cancer as a primary event. Tamoxifen significantly reduced the risk of contralateral breast cancer in all women regardless of age (hazard ratio (HR) 0.5, p = 0.02). In subgroup analysis the risk reduction was most pronounced in patients <40 years of age (HR 0.09, p = 0.02). A risk reduction was also seen in women 40–49 years of age or ?50 years of age, although in these subgroups this did not reach statistical significance. The reduced risk of contralateral breast cancer was persistent during the whole follow-up time.ConclusionIn this randomised trial, adjuvant treatment using tamoxifen for 2 years reduced the incidence of contralateral breast cancer by 50% in all premenopausal women, and by 90% in women <40 years of age. The effect of tamoxifen was not significantly dependent on time.     

蒽环类药物对乳腺癌患者月经状态的影响

目的研究乳腺癌患者年龄及不同蒽环类化疗药物对化疗诱导停经的影响,为临床合理用药提供依据。方法前瞻性研究绝经前乳腺癌患者接受化疗后月经变化情况,比较不同年龄段及使用不同化疗药物的患者月经状态变化的差异。结果137例乳腺癌患者,化疗致闭经（CIA）的发生率为73．72％（101／137）,长期闭经（LCIA）发生率为43．80％（60／137）。40岁以下患者CIA和LCIA的发生率均显著低于40岁以上的患者（X^2=25．32、18．42,P〈0．05）,并且40岁以下组发生CIA后月经恢复率为61．90％（13／21）,明显高于40岁以上组的35．00％（28／80）,差异有统计学意义（X^2=4．99,P=0．025）。40岁以上患者中表柔比星（商品名：法玛新）、表柔比星（商品名：艾达生）、吡柔比星诱导LCIA率差异有统计学意义（X^2=6．92,P=0．031）。结论年龄是CIA的重要因素,40岁以下患者月经受化疗影响较小,停经多为可逆性。40岁以上患者使用不同的蒽环类化疗药物对月经状态的影响差异有统计学意义。     

乳腺癌的辅助化疗

临床研究证实术后辅助化疗能显著降低可手术乳腺癌患者的病死率,提高生存率。目前乳腺癌辅助化疗正朝着特异性、高效性及低毒性方向发展。基于分子遗传学分析的个体化、规范化综合治疗是今后乳腺癌辅助化疗治疗的方向。     

Fertility preservation in women undergoing treatment for breast cancer in the UK: a questionnaire study

Objective.

Fertility preservation is an important survivorship issue for women treated for breast cancer. The aim of this work was to examine the referral practices of health care professionals who treat women with breast cancer in the United Kingdom, and to investigate their understanding and knowledge of the fertility preservation options available.

Method.

An invitation to participate in a confidential, online questionnaire was e-mailed to surgeons, oncologists, and clinical nurse specialists who manage patients with breast cancer in the United Kingdom.

Results.

n = 306 respondents. Factors which influenced whether fertility preservation options were discussed with a patient included the following: patient''s age (78%), final tumor/nodes/metastasis status (37.9%); concern that fertility preservation would delay chemotherapy (37.3%); whether the patient had children (33.5%) or a partner (24.7%); estrogen receptor expression (22.6%), lack of knowledge regarding the available options (20.9%); and concern that fertility preservation would compromise the success of cancer treatment (19.8%). Twenty-seven percent did not know whether fertility preservation was available for their patients on the National Health Service. Nearly half (49.4%) of respondents said that gonadotropin-releasing hormone agonists were used for fertility preservation outside the setting of a clinical trial. Knowledge regarding the available options varied according to different members of the multidisciplinary team, with consultant oncologists better informed than consultant surgeons or clinical nurse specialists (p < .05).

Conclusions.

Many health care professionals have incomplete knowledge regarding the local arrangements for fertility preservation for patients with breast cancer. This may result in patients receiving inadequate or conflicting information regarding fertility preservation.     

含脂质体阿霉素方案在乳腺癌术后辅助化疗中的安全性评价

目的 评价含脂质体阿霉素方案在乳腺癌术后辅助化疗中的安全性。方法 收集2014年9月至2016年8月接受术后辅助化疗的乳腺癌患者29例。化疗方案分别为：3周FAC方案（5-FU 500 mg／m2,脂质体阿霉素30 mg／m2,环磷酰胺500 mg／m2,每21天重复,共3个周期）14例;2周AC方案（脂质体阿霉素30 mg／m2,环磷酰胺600 mg／m2;每14天重复,共4个周期）11例;3周AC方案（脂质体阿霉素30 mg／m2,环磷酰胺600 mg／m2;每21天重复,共4个周期）4例。毒副反应按照NCI CTCAE 4.0.3版本分为1～5级。心脏毒性的评估包括定期检查心电图、心脏超声等。结果 所有患者中最显著的毒副反应为中性粒细胞减少,发生率为79.3％（23／29）;其次为手足综合征和口腔炎,发生率分别为51.7％（15／29）、27.6％（8／29）。AC方案组患者3级手足综合征的发生率为26.7％（4／15）,高于FAC方案组的0（0／14）。本组中无1例左心室射血分数降低10％以上;无1例出现充血性心力衰竭。结论 含脂质体阿霉素方案在乳腺癌术后辅助化疗中是安全的。     

Risk of cancer death by comorbidity severity and use of adjuvant chemotherapy among women with locoregional breast cancer

Objectives

To examine the associations of comorbidity and chemotherapy with breast cancer- and non-breast cancer-related death.

新辅助化疗对局部晚期乳腺癌组织中雌激素受体孕激素受体和人表皮生长因子受体2表达的影响

目的探讨新辅助化疗对晚期乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体2(HER-2)表达的影响。方法收集ⅡB^ⅢB期的局部晚期乳腺癌患者48例,应用免疫组化方法检测ER、PR和HER-2的表达后,给予表阿霉素(EPI)加多西紫杉醇(DOX)方案进行新辅助化疗,3个疗程后行根治手术,将术后标本中ER、PR和HER-2的表达与化疗前表达情况进行对照,分析新辅助化疗对免疫表达的影响。结果新辅助化疗前ER阳性表达率为33.3%,化疗后ER阳性表达率为52.1%;化疗前PR阳性表达率为35.4%,化疗后PR阳性表达率为50.0%。ER和PR阴性表达的患者在新辅助化疗后转为阳性表达的比例高于化疗前阳性转为阴性的比例,但差异没有统计学意义(P>0.05)。新辅助化疗前HER-2阳性表达率为62.5%,化疗后HER-2阳性表达率为52.1%,新辅助化疗后阳性转阴率略高于阴性转阳率,差异无统计学意义(P>0.05)。结论新辅助化疗能使部分乳腺癌组织中ER、PR和HER-2的表达发生改变,为乳腺癌的治疗提供了一定的依据。     

新辅助化疗联合保乳术治疗乳腺癌的疗效观察

目的 探讨新辅助化疗联合保乳术治疗乳腺癌患者的临床疗效及患者雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体-2(HER-2)水平变化情况.方法 选取2018年1月至2020年1月间武警河南总队医院收治的56例乳腺癌患者纳入研究对象,采用随机数表法将患者分为观察组和对照组,每组28例.观察组采用新辅助化疗联合...     

Radiotherapy after high-dose chemotherapy and peripheral blood stem cell support in high-risk breast cancer

To assess the toxicity and efficacy of radiotherapy with respect to locoregional control after adjuvant high-dose chemotherapy for patients with breast cancer. At first, radiotherapy was withheld because of toxicity concerns, but it was introduced in 1995 because of reported high locoregional relapse rates.

Between 1992 and 1998, 40 patients with Stage II–III high-risk breast cancer received adjuvant high-dose chemotherapy consisting of thiotepa, mitoxantrone, and cyclophosphamide and peripheral blood stem cell support after four cycles of induction chemotherapy. The chest wall or breast, as well as the supraclavicular nodes, were irradiated with electrons and photons to a median dose of 50.4 Gy in 20 patients. Six additional patients received only supraclavicular irradiation to a median dose of 50.4 Gy. Acute toxicity was scored clinically. Pulmonary function tests were performed in 14 irradiated patients before high-dose chemotherapy and 1.1–4.4 years (median 1.6) after irradiation. The median follow-up time of living patients was 33 vs. 67 months in irradiated (n = 26) and nonirradiated (n = 14) patients, respectively.

G2 and G3 hematologic toxicity occurred in 1 patient each. No clinical pneumonitis or clinical impairment of lung function was observed. After 1–2 years, the lung function tests showed only minor changes in 4 patients. The 3-year locoregional control rate was 92% in the irradiated patients vs. 58% in the nonirradiated patients (p = 0.049, actuarial analysis).

In this series, adjuvant radiotherapy after adjuvant chemotherapy for breast cancer appeared well tolerated, with improved local regional control and without significant side effects. Longer follow-up and more patient accrual, as well as Phase III trials, are necessary for confirmation.     

Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls

Introduction  The selective estrogen receptor modulator, Tamoxifen (TAM), is one of the most frequently prescribed drugs for the treatment of breast cancer; however, its effects on the cognition of users have not been adequately studied. Although TAM is an effective anti-estrogen that blocks tumour growth in the breast, it could also influence the activity of other target estrogen sites, including the brain. The exact nature of this interaction is unknown. Methods  A cross-sectional design was used to compare cognitive task performance of two treatment groups: 1) women using TAM for the treatment of early breast cancer (n = 23); and 2) age-matched, healthy women not using TAM (n = 23). All participants were pre-menopausal, and recipients of chemotherapy were excluded from the study. Results  It was found that TAM users scored significantly worse than controls on tasks of immediate and delayed visual memory, verbal fluency, immediate verbal memory, visuo-spatial ability, and processing speed. Discussions/Conclusions  Although limited by the lack of baseline data and pre-morbid intelligence measures, the results of this exploratory study suggest that at least in pre-menopausal women, TAM may exert a widespread negative influence on cognitive abilities. Implications for Cancer Survivors  Larger, randomized, prospective trials are required to confirm these results; however, TAM use in pre-menopausal breast cancer may be associated with cognitive difficulties. Knowledge and understanding of these complications will be important for professionals in communicating both the benefits and risks of TAM use in breast cancer survivors.     

Intake of fruits, and vegetables in relation to breast cancer risk by hormone receptor status

Summary The inconsistent associations between fruit and vegetable intake and breast cancer risk may be due to heterogeneity of associations by estrogen (ER) and progesterone receptor (PR) status of the tumors. We evaluated this hypothesis in a large (2,386 cases and 2,503 controls) population-based case-control study in Poland, conducted between 2000 and 2003. We observed significant associations between reduced overall risk of breast cancer and increasing levels of total fruit intake (odds ratio (OR) for highest versus lowest quartile = 0.76, 95%CI = 0.63–0.91; p-trend = 0.01), but not for total vegetable intake (1.13 (0.93–1.37), p-trend = 0.25), after controlling for age, energy intake and known risk factors for breast cancer. The inverse association with total fruit intake was stronger for risk of ER+ (0.69 (0.54–0.88), p-trend = 0.01) than ER− tumors (0.89 (0.67–1.19), p-trend = 0.57) (p-heterogeneity = 0.02). In conclusion, this study suggests that fruit intake might have differential associations for breast tumor subtypes defined by ER status.     

The preference to receive chemotherapy and cancer-related outcomes in older adults with breast cancer CALGB 49907 (Alliance)

Objective

Chemotherapy preference refers to a patient's interest in receiving chemotherapy. This study examined whether chemotherapy preference was associated with toxicity, efficacy, quality of life (QoL), and functional outcomes during and after completion of adjuvant chemotherapy in older women with breast cancer.

Estrogen receptor alpha haplotypes and breast cancer risk in older Caucasian women

Life-long exposure to estrogen is an established risk factor for breast cancer development. The underlying mechanism has been suggested to be the binding of estrogen-to-estrogen receptors in mammary tissue, which in turn promotes the proliferation and differentiation of breast tissue. Polymorphisms and haplotypes in estrogen receptor alpha (ESR1) have been reportedly associated with breast cancer risk; however, the results are not fully consistent. In this study, we investigated breast cancer risk associated with genotypes and haplotypes resulting from four ESR1 single nucleotide polymorphisms (SNPs), rs746432, rs2234693, rs9340799, and rs1801132. Genotyping has been performed on 393 breast cancer cases and 790 randomly selected controls in 1,183 Caucasian women over age 65 from the Study of Osteoporotic Fractures (SOF). We observed an allelic protective effect for SNP rs9340799 with an estimated odds ratio (OR) of 0.82 (95% CI = 0.68–1.00; P = 0.04) after adjustment for age, BMI and hip BMD. A protective effect of this SNP has been reported before in several different studies. We did not replicate the previously reported C–C–A–G haplotype association to breast cancer—the C–C–A–G haplotype from these SNPs was rare in this study (estimated frequency below 0.001% in cases and controls). No other statistically significant associations were observed between ESR1 haplotypes from the same four SNPs and the risk of breast cancer in older Caucasian women.     

乳腺癌患者辅助化疗前后外周血中ＰＩＰｍＲＮＡ表达变化的研究

目的：通过检测乳腺癌患者辅助化疗前后外周血中泌乳素诱导蛋白（ＰＩＰ）ｍＲＮＡ的表达变化,探讨术后辅助化疗对乳腺癌血液微转移的影响。方法：收集沈阳军区总医院肿瘤科２００６年７月～２００７年９月经术后病理证实的乳腺癌患者５０例,在化疗前及接受２～３周期辅助化疗后应用巢式ＲＴ-ＰＣＲ方法检测这些乳腺癌患者外周血中ＰＩＰｍＲＮＡ的表达。另取乳腺纤维腺瘤１０例、健康志愿者１０例、胃癌５例、结直肠癌５例、食管癌５例、肺癌５例、卵巢癌５例作阴性对照。结果：５０例乳腺癌患者外周血标本中,化疗前１７例ＰＩＰｍＲＮＡ阳性的患者,化疗２～３周期后１３例ＰＩＰｍＲＮＡ转为阴性,转阴率７６.５％（１３／１７）,化疗前ＰＩＰｍＲＮＡ表达阴性的患者在化疗后无１例阳性,化疗前后差异有统计学意义（Ｐ＝０.００１）。而对照组４５例外周血标本中均未检出ＰＩＰｍＲＮＡ的表达。ＰＩＰｍＲＮＡ的阳性表达与淋巴结转移、ＴＮＭ分期有关,而与患者年龄、肿瘤大小、ＥＲ、ＰＲ及Ｃ-ｅｒｂＢ-２等表达无关。结论：乳腺癌患者接受术后辅助化疗能够降低血液ＰＩＰｍＲＮＡ的阳性率,有望减少乳腺癌血液微转移的发生。     

Relation of serum levels of estrogen and dehydroepiandrosterone sulfate to hormone receptor status among postmenopausal women with breast cancer

Background: It is hypothesized that breast cancer may consist of heterogeneous diseases with different hormonal environments classified by hormone receptor status. Epidemiologic studies evaluating risk factors for breast cancer by hormone receptor status have supported the hypothesis. However, there are inconsistencies in the risk factor profiles by estrogen receptor (ER) and progesterone receptor (PR) across the studies. To clarify the heterogeneity of the disease, it is necessary to understand not only risk factor profiles but also the biologic characteristics such as the relationships among endogenous sex hormone levels and hormone receptors. Methods: We measured serum levels of estrone (E1), estradiol (E2), dehydroepiandrosterone sulfate (DHEAS), and sex hormone-binding globulin (SHBG) in 142 postmenopausal women aged 50 and over with primary breast cancer who had undergone surgical treatment, and investigated the heterogeneity in the relations of endogenous sex hormone levels to hormone receptor status, using the case-series study method. Subjects were categorized into 3 classes based on tertiles of each hormone level in receptor-negative subjects, and odds ratios (ORs) for receptor-positive status compared with receptor-negative status were computed, taking the lowest category as a reference category. Results: There were clear trends toward higher serum levels of E1, E2, and DHEAS in women with PR+ cancer. The case-series approach revealed that PR+ status might be strongly associated with serum sex hormone levels. In particular, the OR of PR+ was large for a high DHEAS level (OR for the highest category = 4.28). No significant association between serum hormone levels and ER status was observed. Conclusion: The association of serum sex hormone levels with hormone receptor status may differ by PR status, but not by ER status. This finding suggests that PR status may be related to the heterogeneity in hormonal environments associated with breast cancer risk.     

剂量密度化疗在乳腺癌术后辅助化疗中的应用

目的 探讨剂量密度化疗在乳腺癌术后辅助化疗中应用的安全性与可行性。方法 回顾性分析114例因乳腺癌行剂量密度辅助化疗患者的临床资料。结果 114例乳腺癌患者接受了剂量密度辅助化疗,根据复发风险,其中43例接受PE方案（紫杉醇＋表阿霉素）化疗,8例接受TE方案（多烯紫杉醇＋表阿霉素）化疗,36例采用CEF方案（环磷酰胺＋表阿霉素＋5-Fu）,27例采用EC方案（环磷酰胺＋表阿霉素）。除3例患者无法耐受外,其余111例患者均顺利完成所有治疗。Ⅲ度以上不良反应包括粒细胞缺乏（6．3％）、恶心和呕吐（11．7％）、周围神经改变（3．6％）。结论 乳腺癌术后辅助化疗采用剂量密度的方法是安全可行的,其远期疗效尚需进一步观察。