早期(T1-2N1)三阴型乳腺癌根治术后辅助放疗的疗效评估

目的:评估乳腺癌根治术后放疗(post-mastectomy radiation therapy,PMRT)在早期(T1-2N1)三阴型乳腺癌(triple negative breast cancer,TNBC)患者中的治疗价值.方法:回顾性分析SEER数据库中根治术后早期(pT1-2N1)TNBC患者的临床数据.将...     

Prognostic value of cyclin E expression in breast cancer: a meta-analysis

Cyclin E is an important regulator of cell cycle progression. Various studies examined the relationship between cyclin E overexpression with the clinical outcome in patients with breast cancer but yielded conflicting results. Electronic databases updated to May 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between cyclin E overexpression and survival of patients with breast cancer. Survival data were aggregated and quantitatively analyzed. We conducted a final analysis of 7,759 patients from 23 eligible studies and evaluated the correlation between cyclin E overexpression and survival in patients with breast cancer. Combined hazard ratios suggested that cyclin E overexpression had an unfavorable impact on overall survival (OS) (hazard ratio (HR) = 1.30, 95 % confidence interval (CI), 1.12–1.49) and breast cancer-specific survival (BCSS) (HR?=?1.48, 95 % CI, 1.03–1.93), but not disease-free survival (HR?=?1.11; 95 % CI, 0.96–1.27) in patients with breast cancer. Significantly, risks were found among stage I–II breast cancer for (HR?=?1.75; 95 % CI, 1.30–2.19). Cyclin E overexpression is associated with poor OS and BCSS in breast cancer.     

术中放疗对比术后放疗在早期乳腺癌中的生存分析——基于SEER数据库的研究

目的 比较术中放疗(IORT)与术后放疗(PORT)对≥50岁、肿瘤≤3cm、无淋巴结转移的早期女性乳腺癌患者的生存影响及相关预后因素分析。方法 从SEER数据库中获取2010—2015年符合纳入标准的早期乳腺癌患者的资料,分为IORT组及PORT组并进行倾向得分匹配(PSM)。通过Kaplan-Meier曲线获取两组的总生存(OS)和乳腺癌特异性生存(BCSS),Cox模型分析影响预后的因素。结果 PSM后共纳入7068例患者,中位随访32个月,IORT组和PORT组5年OS率分别为96.8%和93.8%。单因素分析显示放疗方式、年龄、组织学分级、T分期、雌激素受体(ER)及孕激素受体(PR)与患者OS有关,组织学分级、T分期、ER、PR以及化疗状态与患者BCSS有关。多因素分析显示IORT较PORT患者OS更好(P=0.020),≥60岁、T2期及ER阴性患者OS较差(P分别为0.003、<0.001、0.001)。组织学Ⅲ-Ⅳ级患者有更差的BCSS (P=0.004)。亚组分析显示IORT较PORT在≥60岁、组织学Ⅲ-Ⅳ级、浸润性导管癌、T2期、ER阳性、PR阳性及未化疗患者中OS获益更多。结论 在审慎选择的低危早期乳腺癌患者中IORT的短期生存不劣于PORT,还需长时间随访的前瞻性研究来进一步证实。     

Low number of examined lymph nodes in node-negative breast cancer patients is an adverse prognostic factor.

BACKGROUND: The aim of the study was to determine whether the number of lymph nodes removed at axillary dissection is associated with recurrence and survival in node-negative breast cancer (NNBC) patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1606 women with pathologically node-negative T1-T3 invasive breast cancer. Median follow-up was 61 months (range 2-251). Potential prognostic factors assessed included: number of axillary lymph nodes examined, age, menopausal status, tumor size, histological type, tumor grade, estrogen receptor(ER), progesterone receptor (PR) and HER2. RESULTS: At 5 years, relapse-free survival (RFS) rate was 85% and breast cancer-specific survival (BCSS) rate was 94%. In univariate analysis, factors significantly associated with lower RFS and BCSS were: fewer than six lymph nodes examined (RFS, P = 0.01; BCSS, P = 0.007), tumor size >2 cm, grade III, negative ER or PR. Statistically significant factors for lower RFS and BCSS in multivariate analysis were: fewer than six lymph nodes examined [RFS, hazard ratio (HR) 1.36, P = 0.029; BCSS, HR 1.87, P = 0.005], tumor size >2 cm, tumor grade III and negative PR. CONCLUSIONS: Examination of fewer than six lymph nodes is an adverse prognostic factor in NNBC because it could lead to understaging. Six or more nodes need to be examined at axillary dissection to be confident of a node-negative status. This may be useful, in conjunction with other prognostic factors, in the assessment of NNBC patients for adjuvant systemic therapy.     

Differences in breast cancer characteristics and outcomes between Caucasian and Chinese women in the US

Chinese breast cancer patients living in the United States (US) can experience different disease patterns than Caucasians, which might allow for predicting the future epidemiology of breast cancer in China. We aimed to compare the clinicopathologic characteristics and outcomes of Caucasian and Chinese female breast cancer patients residing in the US. The study cohort consisted of 3868 Chinese and 208621 Caucasian women (diagnosed from 1990 to 2009) in the US Surveillance, Epidemiology, and End Results (SEER) database. Compared with the Caucasian patients, the US-residing Chinese patients had a younger age at diagnosis and a higher family income, remained married longer, and more frequently lived in metropolitan areas. Other tumor characteristics were similarly distributed between the two races. Compared with the Caucasians, the Chinese patients had a significantly improved overall survival (OS) but similar breast cancer-specific survival (BCSS). Our analysis suggested that US-residing Chinese patients had significant differences in age, family income, marital status and area of residence, compared with their Caucasian counterparts. No significant disparities were noted in BCSS between the two races, whereas the Chinese patients had a significantly better OS. These findings warrant further investigation and should be considered in the screening and treatment of breast cancer.     

Diminished survival in patients with inner versus outer quadrant breast cancers.

PURPOSE: To evaluate the role of breast tumor location on survival in patients with breast cancer. PATIENTS AND METHODS: We evaluated tumor location within the breast on breast cancer-specific survival (BCSS) and overall survival (OS) in patients with invasive breast cancer using the Surveillance, Epidemiology, and End-Results (SEER) registries in the United States. Effects on survival were evaluated according to age, stage, tumor site, tumor size, grade, axillary lymph node status, extent of surgery, and radiotherapy (RT). A multivariate model was used with complete data on 45,880 patients. The median follow-up was 59 months. RESULTS: Patients with outer tumor location demonstrated superior BCSS on Kaplan-Meier analysis for both local stage (node-negative, P <.001) and regional stage disease (node-positive, P =.0002). For BCSS, the hazard ratio (HR) for inner quadrant location compared with outer quadrant was 1.31 (95% confidence interval [CI], 1.19 to 1.37; P <.001); and for OS, the HR was 1.12 (95% CI, 1.05 to 1.17; P <.001). When ER and PR status were included in the model, the HR for inner quadrant location compared with outer quadrant was 1.27 for BCSS (95% CI, 1.16 to 1.40; P <.001) and 1.11 for OS (95% CI, 1.03 to 1.19; P =.004). Patients treated by lumpectomy that received RT had a superior OS compared with patients that did not receive RT in both local (HR, 0.52; 95% CI, 0.48 to 0.61; P <.001) and regional (HR, 0.63; 95% CI, 0.56 to 0.72; P <.001) stage disease. Mastectomy patients with local stage disease that received RT had a diminished OS (HR, 1.24; 95% CI, 1.02 to 1.50; P =.033). CONCLUSION: On multivariate analysis, incorporating data on age, stage, tumor site, tumor size, grade, ER and PR status, axillary lymph node status, extent of surgery, and RT, this SEER registry-based study demonstrates that medial tumor location adversely impacts BCSS and OS.     

Survival benefit from axillary surgery in patients aged 70 years or older with clinically node-negative breast cancer: A population-based propensity-score matched analysis

BackgroundOlder patients with breast cancer have good prognosis and most die from diseases other than breast cancer. Previous studies suggested that the surgical extent in older patients could be reduced. We aimed to compare survival outcomes in patients aged ≥70 years with clinically node-negative breast cancer, based on whether axillary surgery was performed.MethodsA total of 2,995 patients with breast cancer aged ≥70 years who underwent breast surgery were included in the Korean Breast Cancer Registry. Patients were classified into two groups according to the performance of axillary surgery. We used propensity score matching for demographic and treatment factors to minimize selection bias. We compared the 5-year overall survival (OS) and breast cancer-specific survival (BCSS).ResultsAmong 708 patients after 3:1 propensity score matching, 531 underwent breast surgery with axillary surgery and 177 underwent breast surgery alone. Of all patients, 51.7% had T1 stage, and 73.2% underwent mastectomy. Approximately 31.2% of patients received chemotherapy. Among patients who did not undergo axillary surgery, the 5-year OS and BCSS rates were 85.2% and 96.7%, respectively. The hazard ratio of axillary surgery for OS was 0.943 (95% confidence interval 0.652–1.365, p = 0.757), indicating no significant difference between two groups.ConclusionsOur study demonstrates that axillary surgery in a matched cohort of older patients with breast cancer and clinically negative nodes does not provide a survival benefit compared to patients undergoing breast surgery alone. These findings suggest that axillary surgery may be safely omitted in a select group of patients aged ≥70 years with clinically node-negative cancer. Further studies are needed to identify potential candidates for omitting axillary surgery.     

CYP2D6 gene variants: association with breast cancer specific survival in a cohort of breast cancer patients from the United Kingdom treated with adjuvant tamoxifen

Introduction

Tamoxifen is one of the most effective adjuvant breast cancer therapies available. Its metabolism involves the phase I enzyme, cytochrome P4502D6 (CYP2D6), encoded by the highly polymorphic CYP2D6 gene. CYP2D6 variants resulting in poor metabolism of tamoxifen are hypothesised to reduce its efficacy. An FDA-approved pre-treatment CYP2D6 gene testing assay is available. However, evidence from published studies evaluating CYP2D6 variants as predictive factors of tamoxifen efficacy and clinical outcome are conflicting, querying the clinical utility of CYP2D6 testing. We investigated the association of CYP2D6 variants with breast cancer specific survival (BCSS) in breast cancer patients receiving tamoxifen.

Methods

This was a population based case-cohort study. We genotyped known functional variants (n = 7; minor allele frequency (MAF) > 0.01) and single nucleotide polymorphisms (SNPs) (n = 5; MAF > 0.05) tagging all known common variants (tagSNPs), in CYP2D6 in 6640 DNA samples from patients with invasive breast cancer from SEARCH (Studies of Epidemiology and Risk factors in Cancer Heredity); 3155 cases had received tamoxifen therapy. There were 312 deaths from breast cancer, in the tamoxifen treated patients, with over 18000 years of cumulative follow-up. The association between genotype and BCSS was evaluated using Cox proportional hazards regression analysis.

Results

In tamoxifen treated patients, there was weak evidence that the poor-metaboliser variant, CYP2D6*6 (MAF = 0.01), was associated with decreased BCSS (P = 0.02; HR = 1.95; 95% CI = 1.12-3.40). No other variants, including CYP2D6*4 (MAF = 0.20), previously reported to be associated with poorer clinical outcomes, were associated with differences in BCSS, in either the tamoxifen or non-tamoxifen groups.

Conclusions

CYP2D6*6 may affect BCSS in tamoxifen-treated patients. However, the absence of an association with survival in more frequent variants, including CYP2D6*4, questions the validity of the reported association between CYP2D6 genotype and treatment response in breast cancer. Until larger, prospective studies confirming any associations are available, routine CYP2D6 genetic testing should not be used in the clinical setting.     

Overexpression of p53 is correlated with poor outcome in premenopausal women with breast cancer treated with tamoxifen after chemotherapy

The aim of this study was to evaluate the difference in outcomes based on p53 overexpression of patients with breast cancer who received adjuvant therapy following local treatment for invasive ductal carcinoma, not otherwise specified. We analyzed data from 4,683 patients with cancer enrolled in two institutions between 1997 and 2006. We analyzed the correlation between p53 overexpression and relapse, response to adjuvant therapy, breast cancer-specific survival (BCSS), and relapse-free survival (RFS) in patients with primary breast cancer. Overexpression of p53 was noted in 1,091 patients (23.3%). A significant correlation existed between p53 overexpression and poor prognostic factors, an increased frequency of regional recurrence, visceral metastasis, and worse BCSS and RFS. Based upon subgroup analyses, combined age (<35, 35–50, and >50 years) and adjuvant therapy (hormone therapy only, chemotherapy only, and hormone therapy following chemotherapy), the greatest reduction of survival based on p53 overexpression was noted in patients 35–50 years of age who received hormone therapy following chemotherapy (P < 0.05). Multivariate analysis showed that p53 overexpression is an independent prognostic factor in patients treated with hormone therapy and chemotherapy (relative risk for BCSS, 2.003; 95% CI, 1.105–3.631; P = 0.022). The p53-overexpressing patients with breast cancer between 35 and 50 years of age who received tamoxifen following chemotherapy had the greatest adverse effect on outcome. Overexpression of p53 is significantly associated with tamoxifen resistance in premenopausal women with breast cancer.     

Obesity,diabetes, and survival outcomes in a large cohort of early-stage breast cancer patients

BackgroundTo determine the relationship between obesity, diabetes, and survival in a large cohort of breast cancer patients receiving modern chemotherapy and endocrine therapy.Patients and methodsWe identified 6342 patients with stage I–III breast cancer treated between 1996 and 2005. Patients were evaluated according to body mass index (BMI) category and diabetes status.ResultsIn a multivariate model adjusted for body mass index, diabetes, medical comorbidities, patient- and tumor-related variables, and adjuvant therapies, relative to the normal weight, hazard ratios (HRs) for recurrence-free survival (RFS), overall survival (OS), and breast cancer-specific survival (BCSS) for the overweight were 1.18 [95% confidence interval (CI) 1.02–1.36], 1.20 (95% CI 1.00–1.42), and 1.21 (95% CI 0.98–1.48), respectively. HRs for RFS, OS, and BCSS for the obese were 1.13 (95% CI 0.98–1.31), 1.24 (95% CI 1.04–1.48), and 1.23 (95% CI 1.00–1.52), respectively. Subset analyses showed these differences were significant for the ER-positive, but not ER-negative or HER2-positive, groups. Relative to nondiabetics, HRs for diabetics for RFS, OS, and BCSS were 1.21 (95% CI 0.98–1.49), 1.39 (95% CI 1.10–1.77), and 1.04 (95% CI 0.75–1.45), respectively.ConclusionsIn patients receiving modern adjuvant therapies, obesity has a negative impact on RFS, OS, and BCSS; and diabetes has a negative impact on RFS and OS. Control of both may be important to improving survival in obese and diabetic breast cancer patients.     

Population-based validation of the prognostic model ADJUVANT! for early breast cancer.

PURPOSE: Adjuvant! (www.adjuvantonline.com) is a web-based tool that predicts 10-year breast cancer outcomes with and without adjuvant systemic therapy, but it has not been independently validated. METHODS: Using the British Columbia Breast Cancer Outcomes Unit (BCOU) database, demographic, pathologic, staging, and treatment data on 4,083 women diagnosed between 1989 and 1993 in British Columbia with T1-2, N0-1, M0 breast cancer were abstracted and entered into Adjuvant! to calculate predicted 10-year overall survival (OS), breast cancer-specific survival (BCSS), and event-free survival (EFS) for each patient. Individual BCOU observed outcomes at 10 years were independently determined. Predicted and observed outcomes were compared. RESULTS: Across all 4,083 patients, 10-year predicted and observed outcomes were within 1% for OS, BCSS, and EFS (all P > .05). Predicted and observed outcomes were within 2% for most demographic, pathologic, and treatment-defined subgroups. Adjuvant! overestimated OS, BCSS, and EFS in women younger than age 35 years (predicted-observed = 8.6%, 9.6%, and 13.6%, respectively; all P < .001) or with lymphatic or vascular invasion (LVI; predicted-observed = 3.6%, 3.8%, and 4.2%, respectively; all P < .05); these two prognostic factors were not automatically incorporated within the Adjuvant! algorithm. After adjusting for the distribution of LVI, using the prognostic factor impact calculator in Adjuvant!, 10-year predicted and observed outcomes were no longer significantly different. CONCLUSION: Adjuvant! performed reliably. Patients younger than age 35 or with known additional adverse prognostic factors such as LVI require adjustment of risks to derive reliable predictions of prognosis without adjuvant systemic therapy and the absolute benefits of adjuvant systemic therapy.     

PREDICT Plus: development and validation of a prognostic model for early breast cancer that includes HER2

Background:

Predict (www.predict.nhs.uk) is an online, breast cancer prognostication and treatment benefit tool. The aim of this study was to incorporate the prognostic effect of HER2 status in a new version (Predict+), and to compare its performance with the original Predict and Adjuvant!.

Methods:

The prognostic effect of HER2 status was based on an analysis of data from 10 179 breast cancer patients from 14 studies in the Breast Cancer Association Consortium. The hazard ratio estimates were incorporated into Predict. The validation study was based on 1653 patients with early-stage invasive breast cancer identified from the British Columbia Breast Cancer Outcomes Unit. Predicted overall survival (OS) and breast cancer-specific survival (BCSS) for Predict+, Predict and Adjuvant! were compared with observed outcomes.

Results:

All three models performed well for both OS and BCSS. Both Predict models provided better BCSS estimates than Adjuvant!. In the subset of patients with HER2-positive tumours, Predict+ performed substantially better than the other two models for both OS and BCSS.

Conclusion:

Predict+ is the first clinical breast cancer prognostication tool that includes tumour HER2 status. Use of the model might lead to more accurate absolute treatment benefit predictions for individual patients.     

Prognostic value of ABO blood types in young patients with breast cancer; a nationwide study in Korean Breast Cancer Society

The purpose of this study was to investigate the relationship between ABO blood types and breast cancer survival in young Korean patients. This was a retrospective study of 115,474 patients who were surgically treated for primary breast cancer between 1987 and 2011 in Korea. All data were collected by the Korean Breast Cancer Society (KBCS) online breast cancer registry. Each hospital serologically examined the ABO blood types of patients before surgery. There was no significant difference in overall survival (OS) or breast cancer-specific survival (BCSS) among ABO blood types. Type of surgery; T stage; N stage; histologic grade; status of estrogen receptor, progesterone receptor, and HER2; and chemotherapy were significant prognostic factors of OS and BCSS in univariate analysis and multivariate analyses. Compared to women with blood type O, there was a difference in OS and BCSS for blood type A, blood type B, or blood type AB. Compared to blood group non-O, patients with blood group O were more likely to have favorable prognosis when younger than 40 years. Further follow-up studies are necessary to clarify the role of the impact of ABO blood types on prognosis of breast cancer.     

Dose-dependent effect of tamoxifen therapy on endometrial pathologies in postmenopausal breast cancer patients

To assess whether a higher cumulative tamoxifen dose is associated with increased incidence of various types of endometrial pathologies, we compared cumulative dose of tamoxifen treatment as well as demographic characteristics, risk factors for endometrial cancer, transvaginal ultrasonographic endometrial thickness, and various treatments for the primary breast cancer between 159 postmenopausal breast cancer tamoxifen-treated patients without endometrial pathologies (group I) and 67 similar patients with endometrial pathologies (group II). A similar comparison was made between group I patients and similar patients with proliferative endometrium (group IIa), with endometrial hyperplasia (group IIb), with endometrial polyps (group IIc), and with endometrial cancer (group IId). Overall cumulative tamoxifen dose was significantly higher in group II as compared to group I (27.4 ± 33.4 and 17.4±20.2, respectively;P < 0.0252). Transvaginal ultrasonographic endometrial thickness was significantly higher in group II than in group I patients (16.3 ± 11.3 mm and 12.1 ± 6.3 mm, respectively; P < 0.0147). The frequency of diabetes mellitus, of previous postmenopausal bleeding, and of previous exposure to hormone replacement therapy was significantly higher in group II than in group I patients (P < 0.001, P < 0.0001 and P < 0.001, respectively). There were no significant differences in all parameters tested between group I, group IIa, group IIb, group IIc, and group IId. However, there was an obvious trend for higher cumulative tamoxifen dose in patients with benign endometrial pathologies as compared to those without endometrial pathologies or to those with endometrial cancer (Group I = 17.4 ± 20.2g, group IIa = 22.5 ± 18.5g, group IIb = 28.1 ± 20.3g, group IIc = 31.4 ± 42.7g and group IId = 10.4 ± 12.6g).Endometrial pathologies, except for endometrial cancer, are associated with a high cumulative dose of tamoxifen in postmenopausal breast cancer patients.     

Risk of endometrial hyperplasia and carcinoma in breast cancer patients receiving adjuvant tamoxifen

The antiestrogen drug tamoxifen, which is widely used in adjuvant hormone therapy of breast cancer, presents certain risk of causing hyperplasia and endometrial carcinoma. Our clinical data on 1,969 breast cancer patients (stage I-III) (tamoxifen--947; control--1,022) showed a double rise in endometrial carcinoma risk in cases receiving hormone therapy. Endometrial carcinoma incidence in tamoxifen-treated patients was 3% while in the untreated ones--1.6% (p < 0.05). According to the endometrial tissue study in 439 breast cancer patients, proliferative effect of tamoxifen in the form of endometrial hyperplasia was 5--6 times in tamoxifen users. Meanwhile, endometrial carcinoma and hyperplasia risk increased during a much longer exposure to tamoxifen and in combination with such factors as obesity, diabetes mellitus, uterine myoma and estrogen-type colpocytological response. Hence, breast cancer patients need to undergo dynamic follow-up of the endometrium including ultrasonic examination of the small-pelvis organs and cytological study of ecto- and endocervical smears and endometrial aspirates.     

Carcinogenic effects of adjuvant tamoxifen treatment and radiotherapy for early breast cancer.

The occurrence of new primary tumours among postmenopausal patients with primary breast cancer subsequent to adjuvant treatment in Denmark was assessed by linkage to the cancer registry. Following primary surgery, patients in low risk of recurrence (n = 1,828) received no further treatment while patients in high risk randomly received either adjuvant radiotherapy alone (n = 846) or radiotherapy + tamoxifen 30 mg daily for 48 weeks (n = 864). With a median follow-up of 8 years, the incidence of tumours in the contralateral breast was similar among tamoxifen-treated, and non-treated high-risk patients even after adjusting for tumours arising within the first year. The standardized incidence ratio for endometrial cancer was 1.9 (95% confidence interval 0.8-3.9) among tamoxifen treated, the cumulative incidence 1% compared to 0.3% among non-treated patients (p = 0.11). The cumulative risk of non-lymphocytic leukaemia was 0.9% and 0.1% among irradiated and non-irradiated patients respectively (p = 0.4). Prolonged follow-up of tamoxifen-treated patients with regard to new tumours is recommended.     

Second cancers after adjuvant tamoxifen therapy for breast cancer in Japan

Background:Women treated with tamoxifen for breast cancer are atincreased risk of endometrial cancer. We conducted a retrospective cohortstudy to evaluate the risk of second primary cancers after adjuvant tamoxifentherapy for breast cancer in Japan. Patients and methods:The subjects of the study were 6148 womenwho had been diagnosed with stage I, II, or IIIA unilateral primary breastcancer and had received surgical treatment during the period from January 1982through December 1990 at nine institutions in Japan. The information on eachpatient was obtained from medical records or a prospectively compiled computerdatabase at each institution. Results:Of the 6148 women, 3588 (58.4%) were administeredtamoxifen as an adjuvant treatment and 2560 (41.6%) were notadministered. Median follow-up periods were 7.64 years for tamoxifen-treatedpatients and 8.10 years for non-tamoxifen-treated patients, respectively. Theduration of tamoxifen treatment was mostly two years or less (80.7%),and few patients received tamoxifen for more than five years. The cumulativeincidence rates of all second cancers at 10 years were 4.61% and4.09% among tamoxifen-treated and non-tamoxifen-treated patients(P = 0.62), respectively, and the incidence rate ratio (IRR) forall second cancers was 1.06 (95% confidence interval (CI):0.77–1.47) after adjustment of several covariates. The numbers ofendometrial cancers was 9 and 3 among tamoxifen-treated andnon-tamoxifen-treated patients, respectively, and the IRR was 2.37 (95%CI: 0.64–8.77, P = 0.20). Of the 12 patients who developedendometrial cancer, 4 died of cancer (for 3 of them, the cause of death wasbreast cancer), and the other 8 patients were alive as of March 1996. Stomachcancer was the most frequent second cancer and the IRR was 1.34 (95%CI: 0.76–2.38, P = 0.31). There was no substantialincrease in any other type of gastrointestinal cancer such as colorectal andliver cancers among tamoxifen-treated patients. Conclusions:The incidence and risk of second primary cancersassociated with tamoxifen therapy is low. The potential benefit of adjuvanttamoxifen therapy in breast cancer patients outweighs the risk of secondprimary cancers for Japanese breast cancer patients.     

Special subtypes with favorable prognosis in breast cancer: A registry-based cohort study and network meta-analysis

BackgroundWe aimed to explore whether cribriform and adenoid cystic carcinoma had comparable prognoses to mucinous, tubular and papillary carcinoma, which were long recognized as favorable histologies by NCCN guidelines.MethodsA retrospective analysis based on the Surveillance, Epidemiology, and End Results Study (SEER) database (1994–2014) was conducted. The prognostic significance of all clinicopathological factors was calculated using univariate and multivariate analyses. A systematic review based on PubMed and network meta-analysis was conducted.ResultsFrom the SEER database, the histologic subtypes of breast cancer (tubular, cribriform, adenoid cystic, mucinous, and papillary) were sorted by overall survival (OS) (94.4%, 91.6%, 90.8%, 87.6%, and 84.2%, respectively) and tubular, cribriform, mucinous, papillary, and adenoid cystic carcinoma by breast cancer-specific survival (BCSS) (99.4%, 98.4%, 97.7%, 95.2%, and 94.9%, respectively). A network meta-analysis combining 11 studies (886,649 patients) was conducted, which demonstrated consistent outcomes. SEER-based analyses revealed that, among the favorable subtypes, systemic chemotherapy did not improve OS or BCSS in hormone receptor-positive, node-negative patients, validating that these subtypes are generally associated with excellent outcomes, for which systemic chemotherapy may not be warranted.ConclusionsOur data are consistent with guidelines suggesting that the mucinous, tubular, and papillary subtypes of breast cancer have favorable histologies. SEER data and meta-analysis supports this favorable category to include adenoid cystic and cribriform carcinoma, whose OS and BCSS outcomes are comparable to the former three. These findings add to the body of data, suggesting that patients with these histologic subtypes confer excellent prognosis, which may guide optimal therapeutic management strategies.     

Prognosis and clinical presentation of BRCA2-associated breast cancer

54 female breast cancer patients from 22 families with BRCA2 germ line mutations from Sweden and Denmark were compared with 214 age- and date of diagnosis-matched controls identified among breast cancer patients from South Sweden. At diagnosis, BRCA2-associated cases were more often node-positive (N+). OR=1.9 (95% confidence interval (CI)=1.0-3.6; P=0.036), and were more often clinical stage IV: OR=4.6 (95% CI=1.3-17; P=0.021) than the controls. Bilateral disease was also more common among the BRCA2-associated cases: OR=2. 4 (95% CI=1.1-5.3; P=0.027). Breast cancer-specific survival (BCSS) was significantly worse among the BRCA2-associated cases: RR=2.0 (95% CI=1.2-3.4; P=0.010). When stage was corrected for in a multivariate analysis, BCSS was no longer significantly worse for the BRCA2-associated cases: RR=1.6 (95% CI=0.85-3.1). The corresponding effect after correction for bilateral disease was: RR=1.8 (95% CI=1.0-3.1; P=0.034). The unfavourable prognosis in BRCA2-associated breast cancer seems, to a great extent, to be a consequence of the higher clinical stage at diagnosis. The increased presence of bilateral cancers appears to have less impact on survival in this group of hereditary breast cancer. Data presented here needs to be taken into account when counselling healthy carriers of BRCA2 germ line mutations.     

Tamoxifen therapy for breast cancer and endometrial cancer risk.

BACKGROUND: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk. This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. METHODS: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. RESULTS: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1. 07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002). Women with more than 5 years of exposure to tamoxifen had 4. 06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001). Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups. CONCLUSIONS: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories.