Menopausal oestrogens and breast cancer risk: an expanded case-control study

A study among 1960 post-menopausal breast cancer cases and 2258 controls identified through a nation-wide screening program enabled evaluation of effects of oestrogen use on breast cancer risk. Ever use was not associated with increased risk (RR = 1.0), but a significant trend was observed with increasing years of use, with users of 20 or more years being at a 50% excess risk. Elevations associated with long-term use were apparent across all menopause subgroups (natural, ovaries retained, ovaries removed). Hormones exerted particularly adverse effects in those initiating use subsequent to a diagnosis of benign breast disease, particularly long-term users (RR = 3.0, 95% CI 1.6-5.5). There was also some indication that effects predominated among the lower stage tumours, an observation similar to that observed for endometrial cancer. These findings support a role for oestrogens in the aetiology of breast cancer, although risk appears to be enhanced only after extended periods of use, and not to the extent observed for other hormonally-sensitive tumours.     

Relative harms and merits of postoperative radiation following conservative surgery for low risk breast cancer

British Journal of Cancer (2002) 86, 310–311. DOI: 10.1038/sj/bjc/6600005 www.bjcancer.com© 2002 The Cancer Research Campaign     

Cross-linked collagen C- and N-telopeptides for an early diagnosis of bone metastasis from breast cancer

Bone resorption markers have become available for the diagnosis of bone metastasis. We evaluated cross-linked collagen C-and N-telopeptides (ICTP and NTx) in diagnosing bone metastasis from breast cancer. For a threshold of 4.5 ng/ml of 1CTP and 55.0 pmol BCE/micromol of NTx, bone metastasis could be predicted with an accuracy of 84% and 63%, respectively. All the patients who had metastatic lesions, but showed lower than 4.5 ng/ml of ICTP, had a solitary lesion of bone metastasis. Although ICTP is not sensitive enough to detect an early stage of bone metastasis, it is a better biochemical marker than NTx for detecting bone metastasis from breast cancer.     

85例妊娠相关性乳腺癌临床病理特征与诊治的回顾性分析

目的分析妊娠相关性乳腺癌(PABC)患者的临床病理特征、诊断和治疗情况。方法回顾性分析2012年1月至2019年1月中山大学肿瘤防治中心诊治的85例PABC患者的病历资料,评估患者的临床病理特征,分析其诊断模式和治疗情况。年龄、BMI及孕周等指标为偏态分布,用M(P25,P75)表示。用Kaplan-Meier法绘制生存曲线,进一步分析初诊早期PABC患者(初诊时无远处转移)乳腺手术后的DFS和初诊晚期患者(初诊时有远处转移)的无进展生存时间。结果85例患者诊断为PABC的年龄为33(30,36)岁,BMI为22.5(20.5,24.0)kg/m²。4例患者有乳腺癌家族史。在85例患者中,48.2%(41/85)诊断时处于妊娠期,51.8%(44/85)诊断时处于产后1年内。在妊娠期诊断的患者中,孕周为28(19,32)周,而在产后诊断的患者中,诊断时间为产后4(1,8)个月。病理方面,67例患者为浸润性导管癌,4例浸润性小叶癌,1例黏液癌,6例混合性癌,4例其他类型癌,3例未知;38例患者组织学分级为3级,26例2级,21例组织学分级不明。54例患者为ER/PR阳性,30例HER-2阳性。luminal B1型、三阴型、luminal B2型、HER-2阳性型和luminal A型分别为25、22、21、9、5例,3例分子分型未知。TNM分期Ⅰ期、Ⅱ期、Ⅲ期及Ⅳ期患者分别为10、27、27、16例,另有5例分期未知。59例患者的诊断模式为查体+超声+穿刺活组织检查。本研究有74例患者接受手术,包括59例改良根治术,8例区段切除术+腋窝淋巴结清扫,3例乳房全切术加前哨淋巴结活组织检查,4例区段切除术+前哨淋巴结活组织检查。37例患者仅接受化疗,22例接受化疗+内分泌治疗,11例进行化疗+靶向+内分泌治疗,11例接受化疗+靶向治疗,3例仅接受内分泌治疗,另有1例治疗信息未知。化疗多采用以蒽环类和紫杉类为主的化疗方案。45例患者接受放射治疗且均在产后。在妊娠期诊断的患者中,27例在妊娠期未进行治疗,10例接受新辅助化疗,4例接受了手术治疗。85例患者的随访时间为23.6(12.8,46.4)个月,其中,失访7例(8.2%)。初诊早期PABC患者62例,DFS为36.0个月(95%CI:29.2~42.8个月);初诊晚期PABC患者16例,PFS为14.5个月(95%CI:5.0~23.9个月)。结论对于PABC患者,手术或化疗是相对安全的治疗选择。     

妊娠期乳腺癌的研究现状及进展

妊娠期乳腺癌是指妊娠期间及分娩后1年内确诊的乳腺癌。妊娠期乳腺癌患者的临床预后与肿瘤的生物学特征及肿瘤分期相关，妊娠不是导致不良预后的独立危险因素。但妊娠期激素水平变化使得乳腺组织较为致密，妊娠期乳腺癌早期易被漏诊。由于许多诊断治疗方式可能影响胎儿的正常发育，妊娠增加了乳腺癌治疗方案制定的复杂性。妊娠期乳腺癌需多学科专家根据肿瘤生物学特征、肿瘤分期、孕周及患者和家属意愿等共同制定综合治疗策略。     

14例妊娠期乳腺癌的诊疗体会及文献回顾

目的探讨妊娠期乳腺癌综合治疗的方法及特点。方法回顾性分析14例妊娠期乳腺癌患者的临床资料,探讨临床综合治疗的特点和体会并文献分析。结果 14例妊娠期乳腺癌患者中Ⅱ期6例,Ⅲ期7例,Ⅳ期1例;随访结果显示3例患者死亡,3例患者失访,8例患者无病生存。结论妊娠期乳腺癌恶性程度较高,预后较差,除胎儿因素外,其治疗原则与非妊娠期乳腺癌相同;在治疗中需要综合考虑胎儿安全及患者因素,根据具体情况制定合适的诊疗方案。     

Screening of populations at high risk for breast cancer

The approach to screening patients at high risk for breast cancer has thus far been challenging to standardize, given limited high-level evidence in this population. The approach has evolved given the development of more effective screening modalities, including digital breast mammography, magnetic resonance imaging, and other emerging technologies. This review will discuss identification of high-risk patients, approaches to genetic counseling and testing, and evidence behind screening modalities and algorithms in this special population.     

Chemoprevention of breast cancer for women at high risk

Breast cancer remains the second most common cause of cancer death in the United States. Several studies have identified cohorts of women at higher than average risk to develop this disease. These are women who are exposed to high levels of endogenous or exogenous estrogens, those with a family history of breast cancer, and those who harbor benign breast disease or genetic mutations that predispose to breast cancer. In this population group, adapting a chemoprevention strategy to decrease the risk of developing overt disease is a strong consideration. To this end, tamoxifen is the most studied agent to date. This article describes high-risk categories that predict future development of invasive breast cancer, summarizes the currently available data to support the use of tamoxifen for chemoprevention, and discusses the adverse effects of tamoxifen, as well as measures to anticipate and monitor for possible adverse outcomes.     

Stage at diagnosis and mortality in women with pregnancy-associated breast cancer (PABC)

Converging evidence indicates that women with pregnancy-associated breast cancer (PABC) have increased mortality compared to women with breast cancer not diagnosed near pregnancy (non-PABC). Our aim was to investigate if the stage distribution differs between PABC and non-PABC and if stage at diagnosis can explain the poorer prognosis observed among women with PABC. We identified 3,282 breast cancers in women aged 15–44 years at diagnosis for whom staging data (tumor size, nodal involvement, metastasis) were available in the Swedish Cancer Register between 2002 and 2009. Information on reproductive history and vital status was obtained from the Multi-Generation Register and the Cause of Death Register. PABC was defined as breast cancers diagnosed during pregnancy and up to 2 years after delivery (n = 317). Non-PABC was defined as cases diagnosed before pregnancy or more than 2 years postpartum. Stage distributions were compared between PABC and non-PABC, and mortality rates were modeled using Cox regression. Compared to women with non-PABC, the mortality was almost 50 % higher in women with PABC [unadjusted hazard ratio (HR) 1.47 (95 % CI 1.04–2.08)], a difference which was reduced after adjustment for age and calendar year of diagnosis [HR 1.27 (95 % CI 0.88–1.83)]. Although advanced stage of breast cancer at diagnosis was more common among PABC than among non-PABC, further adjustment for stage only slightly reduced the HR [1.22 (95 % CI 0.84–1.78)]. The difference in mortality between PABC and non-PABC was more pronounced among women above 35 years and among women with PABC diagnosed within 1 year postpartum. Age, rather than stage at diagnosis, appears to act as the principal driver of the increased mortality observed in women with PABC. However, these findings do not preclude an untoward influence on mortality by pregnancy-associated factors affecting tumor aggressiveness and progression.     

Prophylactic surgery for women at high risk for breast cancer

Women at high risk for the development of breast cancer have several options open to them including increased cancer surveillance, prophylactic mastectomy and/or oophorectomy, and chemoprevention. We consider high-risk women to be those with known BRCA mutations or a strong family history characterized by multiple relatives with breast cancer, early age at diagnosis, and in some families, ovarian cancer. We present existing data regarding prophylactic surgery for these women. Essentially, a woman at high risk for breast cancer may choose to undergo bilateral prophylactic mastectomy, with or without reconstruction. For patients who have a known breast cancer, contralateral mastectomy is also an option. Finally, for women in families with a strong incidence of ovarian cancer, prophylactic oophorectomy can be considered.     

Benign breast biopsy diagnosis and subsequent risk of breast cancer.

BACKGROUND: We examine benign breast biopsy diagnoses as reported by community pathologists in New Mexico and investigate associations with future breast cancer development. METHODS: Using data collected between 1992 and 2000 by the New Mexico Mammography Project and cancer data through 2003 from the New Mexico Tumor Registry, we calculated breast cancer rates following 14,602 benign breast biopsies for women ages 30 to 89 years. For comparison, we also calculated the breast cancer rate following 215,283 normal screening mammograms. Hazard ratios (HR) are presented. RESULTS: We identified 480 subsequent breast cancer diagnoses among 14,602 women with benign breast biopsies and 4,402 breast cancer diagnoses among 215,283 women with mammograms assigned a "negative" or "benign finding" assessment. Histologic diagnoses in absence of atypia had an age-adjusted HR of 1.95 [95% confidence interval (95% CI), 1.77-2.15]. Among low-risk histologic diagnoses, the strongest associations with subsequent breast cancer development included adenosis, apocrine metaplasia, calcifications, and ductal hyperplasia. Fibroadenoma, inflammation, and cysts did not exhibit an association with breast cancer development. Women with low-risk diagnoses and breast tissue characterized as fatty or with scattered densities had a HR of 2.09 (95% CI, 1.68-2.60), whereas women with low-risk histologic diagnoses and dense breasts had a HR of 3.36 (95% CI, 2.83-3.99). CONCLUSIONS: The observed breast cancer occurrence contributes to evidence of increased risk following benign biopsy. The risk associated with histologic diagnoses in absence of atypia was twice the risk experienced by women with normal mammogram evaluations and may be modified by breast density.     

Evaluation of a breast cancer risk prediction model expanded to include category of prior benign breast disease lesion

BACKGROUND:

Benign breast diseases (BBD) encompass several histologic subtypes with various risks of subsequent breast cancer. Information on previous benign breast disease biopsies has been incorporated into breast cancer risk prediction models; however, the type of histologic lesion has not been taken into account. Given the substantial heterogeneity in breast cancer risk dependent on the type of benign lesion, the authors evaluated whether incorporating this level of detail would improve the discriminatory power of risk classification models.

METHODS:

By using data from the Nurses' Health Study, a breast cancer nested case‐control study (240 cases; 1036 controls), the authors determined predictors of categories of BBD lesions and developed imputation models. The type of BBD, imputed for each cohort member who reported a diagnosis, was added to a modified version of the Rosner‐Colditz breast cancer risk prediction model.

RESULTS:

Compared with the model that included only previous BBD (yes/no), the model that included categories of BBD was significantly improved (P < .0001). Overall, including the category of BBD increased the concordance statistic from 0.628 to 0.635. By using risk reclassification, inclusion of the type of BBD resulted in a 17% increase in incidence per increase of 1 risk decile, holding the model without BBD type risk decile constant.

CONCLUSIONS:

Although the current data suggested that the inclusion of BBD category may improve breast cancer risk classification, the clinical utility of such a model will depend on the consistency of histologic classification of benign breast disease lesions. Cancer 2010. © 2010 American Cancer Society.     

Risks for familial and contralateral breast cancer interact multiplicatively and cause a high risk

The reasons for the high risk of contralateral breast cancer are not understood, although polygenic mechanisms have been suggested to be involved. The nationwide Swedish Family-Cancer Database was used to examine the interaction of the risks for contralateral and familial cancer. Relative risks were separately determined for contralateral and familial breast cancers, and these were tested for additive and multiplicative interactions. The Database contained information on 102,176 first breast cancers. Familial risk for breast cancer was 1.76 and the risk for contralateral breast cancer was 3.40, or 5.80 when extrapolated to two breasts. When women had a family history, the risk for contralateral breast cancer was remarkably high, 5.48, or 9.96 when the risk was extrapolated to two breasts, almost identical with 10.21, which was predicted by the multiplicative model. Although the data do not rule out polygenic mechanisms, they suggest that epigenetic imprinting events may be involved for the contralateral breast cancer.