The safety of breast-conserving therapy in patients with breast cancer aged < or = 40 years

BACKGROUND: The objectives of this study were to study the probability of local control after breast-conserving therapy (BCT) in a large population of patients with early-stage breast cancer aged < or = 40 years and to determine which factors had prognostic value. METHODS: All patients (n = 758) aged < or = 40 years with clinical stage I or II breast cancer who underwent BCT in general hospitals in the southern part of the Netherlands between 1988 and 2002 were selected for the current analysis. BCT included local excision of the tumor followed by irradiation of the breast. Of 758 patients, 329 patients (43%) received adjuvant systemic treatment, and 36 patients (5%) underwent a microscopically incomplete excision. The median follow-up was 8.5 years. RESULTS: During follow-up, 95 patients developed a local recurrence without evidence of distant disease at the time the recurrence was diagnosed. Contralateral breast cancer was diagnosed in 59 patients. The 5- and 10-year actuarial local recurrence rates were 9.0% (95% confidence interval [95% CI], 6.6-11.4%) and 17.9% (95% CI, 14.1-21.7%), respectively. In a multivariate analysis, adjuvant systemic treatment reduced the risk of local recurrence (hazards ratio [HR], 0.47; 95% CI, 0.28-0.78) and contralateral breast cancer (HR, 0.46; 95% CI, 0.24-0.87) by >50%. CONCLUSIONS: The risk of local recurrence in young patients who underwent BCT was reduced strongly by using adjuvant systemic treatment. This finding may provide an argument if favor of advising the use of systemic treatment for all patients aged < or = 40 years who undergo BCT.     

Prognostic influence of BCL2 expression in breast cancer

Although BCL2 has occasionally been suggested as a candidate prognostic factor for breast cancer, it is still not accepted as a prognostic factor. We attempted to validate the role of BCL2 as a prognostic factor of breast cancer. Data on 7,230 primary breast cancer patients from the Seoul National University Hospital Breast Care Center were analyzed. Three current prognostic models, including the St. Gallen model, the Nottingham prognostic index (NPI) model and the TNM model, were used for analysis of the prognostic influence of BCL2. The positive BCL2 group showed more favorable features with regard to clinicopathologic parameters than the BCL2 negative group and a strong correlation was observed between BCL2 and the hormonal receptor. The positive BCL2 group showed better prognosis in overall survival and disease free survival (log-rank test, both p < 0.001), even in all subgroups, than the BCL2 negative group. BCL2 was a significant prognostic factor in both univariate (hazard ratio [HR], 0.361; 95% confidence interval (CI), 0.306-0.426; p < 0.001) and multivariate analyses (HR, 0.417; 95% CI, 0.417-0.705; p < 0.001). BCL2 had a strong influence on the established prognostic models, including the St. Gallen model, the NPI model and the TNM model. BCL2 was a powerful independent prognostic factor for breast cancer and had a strong influence on the current prognostic models. Favorable clinicopathologic features and a strong correlation with the hormonal receptor are suggested as the causes of superior survival in patients with BCL2 positive breast cancer.     

Nottingham Prognostic Index is an Applicable Prognostic Tool in Non-Metastatic Triple-Negative Breast Cancer

Introduction: Triple-negative breast cancer (TNBC) is characterized by a poor prognosis due to high mortalityand early relapse, requiring the study of its prognostic factors. Tumor size, histological grade and lymph node statusrepresent important parameters that are widely studied in breast cancer, and are retained as prognostic factors by severalinternational guidelines. The Nottingham team combined these parameters into a prognostic score called the Nottinghamprognostic index (NPI). In this study, we investigated the influence of NPI on outcomes in non metastatic TNBC.Methodology: This retrospective cohort study included all female patients with non metastatic TNBC who receivedtreatment at the Regional Oncology Center Hassan II Oujda - Morocco, between January 2009 and December 2011.The prognostic impact of the NPI on the survival curves at 5 years was studied using multivariate Cox proportionalhazards models. Results: The analysis of the data involved 98 patients, 39 patients (39.8%) were classed in the poorprognosis group with a NPI > 5.4. The Overall survival (OS) and Disease free survival (DFS) rates at 5 years, in thisgroup, were 70 and 55.6 % respectively. After adjusting for clinic-pathological variables, a NPI > 5.4 was associated withmortality (HR: 2.598, 95% CI: 1.423 – 4.744, p = 0.002) and disease progression (HR: 2.512, CI to 95%: 1.496 – 4.219,p <0.001) in patients with non-metastatic TNBC. Conclusion: This retrospective cohort analysis showed that NPI wasan independent prognostic factor for OS and DFS at 5 years in women with non metastatic TNBC. Once validated, theimpact of this score on survival outcomes could be considered in the clinical management of TNBC.     

Survival Time and Prognostic Factors for Breast Cancer among Women in North-East Peninsular Malaysia

Background: Breast cancer is the most common malignant disease and the leading cause of cancer death amongwomen globally. This study aimed to determine the median survival time and prognostic factors for breast cancerpatients in a North-East State of Malaysia. Methods: This retrospective cohort study was conducted from January tillApril 2017 using secondary data obtained from the state’s cancer registry. All 549 cases of breast cancer diagnosedfrom 1st January 2007 until 31st December 2011 were selected and retrospectively followed-up until 31st December2016. Sociodemographic and clinical information was collected to determine prognostic factors. Results: The average(SD) age at diagnosis was 50.4 (11.2) years, the majority of patients having Malay ethnicity (85.8%) and a histology ofductal carcinoma (81.5%). Median survival times for those presenting at stages III and IV were 50.8 (95% CI: 25.34,76.19) and 6.9 (95% CI: 3.21, 10.61) months, respectively. Ethnicity (Adj. HR for Malay vs non-Malay ethnicity=2.52;95% CI: 1.54, 4.13; p<0.001), stage at presentation (Adj. HR for Stage III vs Stage I=2.31; 95% CI: 1.57, 3.39; p<0.001and Adj. HR for Stage IV vs Stage I=6.20; 95% CI: 4.45, 8.65; p<0.001), and history of surgical treatment (Adj. HRfor patients with no surgical intervention=1.95; 95% CI: 1.52, 2.52; p<0.001) were observed to be the statisticallysignificant prognostic factors associated with death caused by breast cancer. Conclusion: The median survival timeamong breast cancer patients in North-East State of Malaysia was short as compared to other studies. Primary andsecondary prevention aimed at early diagnosis and surgical management of breast cancer, particularly among the Malayethnic group, could improve treatment outcome.     

Bcl-2 is a prognostic marker in breast cancer independently of the Nottingham Prognostic Index.

PURPOSE: Prognostication of breast cancer using clinicopathologic variables, although useful, remains imperfect. Many reports suggest that gene expression profiling can refine the current approach. Alternatively, it has been shown that panels of proteins assessed by immunohistochemistry might also be useful in this regard. We evaluate the prognostic potential of a panel of markers by immunohistochemistry in a large case series to establish if either a single marker or a panel could improve the prognostic power of the Nottingham Prognostic Index (NPI). We validated the results in an independent series. Experimental Design and RESULTS: The expression of 13 biomarkers was evaluated in 930 breast cancers on a tissue microarray. Eight markers [estrogen receptor (ER), progesterone receptor (PR), Bcl-2, cyclin E, p53, MIB-1, cytokeratin 5/6, and HER2] showed a significant association with survival at 10 years on univariate analysis. On multivariate analysis that included these eight markers and the NPI, only the NPI [hazard ratio (HR), 1.35; 95% confidence interval (95% CI), 1.16-1.56; P = 0.0005], ER (HR, 0.59; 95% CI, 0.39-0.88; P = 0.011), and Bcl-2 (HR, 0.68; 95% CI, 0.46-0.99; P = 0.055) were significant. In a subsequent multivariate analysis that included the NPI, ER, and Bcl-2, only Bcl-2 (HR, 0.62; 95% CI, 0.44-0.87; P = 0.006) remained independent of NPI (HR, 1.50; 95% CI, 1.16-1.56; P = 0.004). In addition, Bcl-2, used as a single marker, was more powerful than the use of a panel of markers. Based on these results, an independent series was used to validate the prognostic significance of Bcl-2. ER and PR were also evaluated in this validation series. Bcl-2 (HR, 0.83; 95% CI, 0.71-0.96; P = 0.018) retained prognostic significance independent of the NPI (HR, 2.04; 95% CI, 1.67-2.51; P < 0.001) with an effect that was maximal in the first 5 years. CONCLUSION: Bcl-2 is an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis.     

Effect of Primary Systemic Therapy on PD-1, PD-L1, and PD-L2 mRNA Expression in Advanced Breast Cancer

Objective: The association between PD-1, PD-L1, and PD-L2 expression and prognosis has been extensively studied in various cancers but remained controversial in breast cancer. Besides, little is known about the prognostic value of PD-1, PD-L1, and PD-L2 upregulation or downregulation following systemic therapy (chemotherapy and hormonal therapy) in breast cancer. Therefore, we aim to investigate the change of PD-1, PD-L1, and PD-L2 expression in mRNA level after primary systemic therapy in breast cancer patients and its clinical implications. Methods: Expression of PD-1, PD-L1, and PD-L2 mRNA were measured before-after chemotherapy and hormonal therapy with real-time PCR in 80 advanced breast cancer patients. The correlation between alteration of PD-1, PD-L1, and PD-L2 expression and clinicopathological characteristics as well as overall survival was also statistically analyzed. Results: Chemotherapy and hormonal therapy altered PD-1, PD-L1, and PD-L2 expression in breast cancer with most patients have an increase expression. As much as 57.1%, 62.9% and 60% patients have an increase PD-1, PD-L1, and PD-L2 expression after chemotherapy, while 60%, 60%, and 64% patients have an increase PD-1, PD-L1, and PD-L2 expression after hormonal therapy. Alteration of PD-1, PD-L1, and PD-L2 expression was not correlated with all clinicopathological characteristics. Increase in PD-1, PD-L1, and PD-L2 expression was significantly associated with better OS (p=0.031, p=0.019, and p=0.019 for PD-1, PD-L1, and PD-L2, respectively), which remained significant in multivariate analysis including age, stage, primary systemic therapy, histology grade, subtype and primary tumor histology (HR PD-1 0.5 (95% CI 0.28-0.88) p=0.031; HR PD-L1 0.43 (95% CI 0.24-0.8) p=0.019; HR PD-L2 (95% CI 0.24-0.87) p=0.019).  Conclusion: Expression of PD-1, PD-L1, and PD-L2 in breast cancer patients is mostly enhanced after chemotherapy and hormonal therapy, and the enhancement is associated with good OS. This result revealed the potential of measuring PD-1, PD-L1, and PD-L2 mRNA expression in predicting clinical outcome.     

Prognostic factors for recurrent breast cancer patients with an isolated,limited number of lung metastases and implications for pulmonary metastasectomy

BACKGROUND:

The aim of this study was to evaluate the clinical treatment outcomes of recurrent breast cancer with a limited number of isolated lung metastases, and to evaluate the role of pulmonary metastasectomy.

METHODS:

The authors consecutively enrolled 140 recurrent breast cancer patients with isolated lung metastasis from 1997 to 2007 in Seoul National University Hospital and retrospectively analyzed 45 patients who had <4 metastatic lesions.

RESULTS:

Fifteen patients had pulmonary metastasectomy followed by systemic treatment (pulmonary metastasectomy group), and 30 received systemic treatment alone (nonpulmonary metastasectomy group). The 3‐year progression‐free survival (PFS) and 4‐year overall survival (OS) was significantly longer in the pulmonary metastasectomy group than in the nonpulmonary metastasectomy group (3‐year PFS, 55.0% vs 4.5%, P < .001; 4‐year OS, 82.1% vs 31.6%, P = .001). In multivariate analysis, a disease‐free interval (DFI) of <24 months (hazard ratio [HR], 4.53; 95% CI, 1.72‐11.90), no pulmonary metastasectomy (HR, 9.52; 95% CI, 3.34‐27.18) and biologic subtypes such as human epithelial growth factor receptor‐2 positive (HR, 3.00; 95% CI, 1.04‐8.64) and triple negative (HR, 3.92; 95% CI, 1.32‐11.59) were independent prognostic factors for shorter PFS.

CONCLUSIONS:

The authors' results demonstrated that DFI and biologic subtypes of tumor are firm, independent, prognostic factors for survival, and pulmonary metastasectomy can be a reasonable treatment option in this population. Further prospective studies are warranted to evaluate the role of pulmonary metastasectomy. Cancer 2010. © 2010 American Cancer Society.     

Can a subgroup of node-negative breast carcinoma patients with T1-2 tumor who may benefit from postmastectomy radiotherapy be identified?

PURPOSE: To determine a subgroup of T1-2N0 breast carcinoma patients at high risk for local recurrence. METHODS AND MATERIALS: In this retrospective study, univariate and multivariate prognostic factor analyses for local recurrence and distant recurrence were carried out in 502 patients. RESULTS: During the median observation time of 77 months (range, 24-191 months), 14 patients (2.8%) had local recurrence and 55 (11.0%) had distant recurrence. Tumor size (continuous, p = 0.03; hazard ratio [HR] 1.2; 95% confidence interval [CI], 1.1-1.7), grade (p = 0.01; HR, 2.4; 95% CI, 1.2-5.0), lymphatic vascular invasion (LVI) (p = 0.01; HR, 10.0; 95% CI, 2.4-17.3), estrogen receptor status (p = 0.01; HR, 6.3; 95% CI, 2.0-23.0) and cErbB2 status (p = 0.01; HR, 10.0; 95% CI 1.8-87.5) were strongly associated with distant recurrence. Tumor size (< or =2 cm vs. >2 cm; p = 0.05; HR, 5.4; 95% CI, 1.2-28.0) and LVI (p = 0.004; HR, 9.0; 95% CI, 2.0-41.0) in patients aged < or =40 years, and tumor size (< or =3 cm vs. >3 cm; p = 0.05; HR 8.6; 95% CI 1.3-75.0), LVI (p = 0.007; HR, 18.0; 95% CI, 2.1-153.0), and grade (p = 0.05; HR, 7.0; 95% CI, 1.2-63.0) in patients aged >40 years were the most important predictive factors for local recurrence. CONCLUSIONS: Among breast carcinoma patients, young patients with tumor size >2 cm and LVI and older patients with tumor size >3 cm, LVI, and high-grade tumor had a high risk of local recurrence.     

Immediate postmastectomy reconstruction is associated with improved breast cancer‐specific survival

BACKGROUND:

Although immediate breast reconstruction is increasingly offered as part of postmastectomy psychosocial rehabilitation, concerns remain that it may delay adjuvant therapy or impair detection of local recurrence. No single population‐based study has examined the relationship between immediate breast reconstruction and breast cancer‐specific survival.

METHODS:

By using data from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries, breast cancer‐specific survival was compared for female unilateral mastectomy patients who did or did not undergo immediate breast reconstruction. Cox proportional hazards models were fitted, adjusting for known demographic and disease severity variables and stratifying on reconstruction type (implant or autologous) and age.

RESULTS:

Improved breast cancer‐specific survival was observed among all immediate breast reconstruction patients compared with patients who underwent mastectomy alone (hazard ratio [HR] = 0.74; 95% confidence interval [CI], 0.68 to 0.80). Implant reconstruction patients below 50 years of age demonstrated the greatest apparent survival benefit (HR = 0.47; 95% CI 0.28 to 0.80). Similarly, autologous reconstruction was associated with improved cancer‐specific survival among patients below the age of 50 (HR = 0.58; 95% CI, 0.42 to 0.80) and between ages 50 to 69 (HR = 0.61; 95% CI, 0.43 to 0.85).

CONCLUSIONS:

Immediate breast reconstruction is associated with decreased breast cancer‐specific mortality, particularly among younger women. We believe this association is more likely attributable to imbalances in socioeconomic factors and access to care than to inadequate adjustment for tumor characteristics and disease severity. Further research is needed to identify additional prognostic factors responsible for the improved cancer survival among women undergoing immediate postmastectomy reconstruction. Cancer 2009. © 2009 American Cancer Society.     

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.     

Pre-diagnostic alcohol consumption and postmenopausal breast cancer survival: a prospective patient cohort study

Study results on the association of alcohol consumption with breast cancer survival are inconsistent, partly due to the use of different survival outcomes. We assessed the association of pre-diagnostic alcohol consumption with survival and recurrence in a prospective cohort study in Germany including 2,522 postmenopausal breast cancer patients aged 50?C74?years. Patients were diagnosed between 2001 and 2005 and vital status, causes of death, and recurrences were verified through the end of 2009. Cox proportional hazards models were stratified by age at diagnosis and study center and adjusted for relevant prognostic factors. Alcohol consumption was non-linearly associated with increased breast cancer-specific mortality [e.g., ??12 vs. <0.5?g/day: hazard ratio (HR)?=?1.74, 95?% confidence interval (CI): 1.13, 2.67]. Results were independent of estrogen receptor status. A non-significantly decreased risk of mortality due to other causes was found (??12 vs. <0.5?g/day: HR?=?0.67, 95?% CI: 0.35, 1.29). Alcohol consumption was not associated with overall mortality (??12 vs. <0.5?g/day: HR?=?1.28, 95?% CI: 0.90, 1.81) and breast cancer recurrence (??12 vs. <0.5?g/day: HR?=?1.08, 95?% CI: 0.73, 1.58). In conclusion, our findings show that consumption of alcohol before diagnosis is non-linearly associated with increased breast cancer-specific mortality but may be associated with decreased risk of mortality due to other causes.     

Stage IV breast cancer: a population‐based study about prognostic factors according to HER2 and HR status

We aim to describe trends in net survival (NS) and to assess the prognostic factors among women with de novo metastatic breast cancer (MBC) according to human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR) status. Data on women suffering from de novo MBC and diagnosed from 1998 to 2009 were provided by the Côte‐d'Or breast cancer registry. NS was described using the Pohar Perme estimator and prognostic factors were investigated in a generalised linear model. We identified 232 patients (mean age = 64.7). Median NS was 29.2 months, 1‐ and 5‐year NS were 76% and 26% respectively. The survival trend in patients with HER2‐positive tumours who did not receive trastuzumab was similar to that in women with triple‐negative tumours. A higher relative excess risk of death by cancer was observed for high‐grade tumours [RER, relative excess rates = 1.76 (95% CI, confidence intervals: 1.17–2.62) for Scarff Bloom Richardson grade 3 vs. 1 + 2], while a lower risk was observed for luminal tumours [RER = 0.49 (95% CI: 0.27–0.89)] and HER2‐positive tumours treated with trastuzumab [RER = 0.28 (95% CI: 0.14–0.59)], both compared with triple‐negative tumours. Surgery of the primary tumour was associated with better survival [RER = 0.43 (95% CI: 0.28–0.68)]. With half of the women dead before 29 months, stage IV breast cancer still has a bleak outlook. Progress should continue with new target therapies for both HR and HER2 receptors.     

Prognostic role of matrix metalloproteinase 9 in early breast cancer

MMP9 is involved in extracellular matrix degradation during various physiological and pathological conditions, including tumorigenesis. The present study aimed to assess the prognostic role of intratumoral MMP9 and to determine its association with circulating tumor cells (CTCs) in patients with early breast cancer. A total of 318 patients with primary breast cancer (PBC) were enrolled into the present study. Specimens were subjected to immunohistochemistry analysis, using the MMP9 monoclonal antibody. MMP9 expression was scored using a weighted histoscore (WH). The results demonstrated that the mean WH ± SEM for MMP9 expression was significantly higher in breast tumor cells compared with tumor associated stromas (132.0±5.2 vs. 50.8±3.7; P<0.00001). Furthermore, a positive association was observed between MMP9 expression, the hormone positive status and proliferation index of analysed breast cancer tumour cells. Notably, the prognostic role of MMP9 was not observed in tumor cells [hazard ratio (HR) =0.96; 95% confidence interval (CI), 0.58–1.59; P=0.864] or tumor associated stroma (HR=1.29; 95% CI, 0.60–2.78; P=0.547). Subgroup analysis demonstrated that patients that were HR negative or triple negative, with low MMP9 expression in tumor cells and stroma had a significantly improved disease-free survival than patients with high MMP9 expression. Taken together, the results of the present study demonstrated that high MMP9 expression in PBC was associated with favorable tumor characteristics. However, the prognostic value of MMP9 was limited to only the HR negative and CTC epithelial-to-mesenchymal transition positive subgroups. Thus, analyzing MMP9 tumor expression may help identify patients with increased risk of disease recurrence in these subgroups.     

Diet and risk for breast cancer recurrence and survival

Dietary factors may influence the risk for breast cancer and also the prognosis following diagnosis and treatment. The aim of this study was to assess whether self-reported prediagnosis diet or other patient factors associated with breast cancer incidence were predictive of recurrence and survival. Patients (n=149) diagnosed with primary breast cancer between 1989 and 1991 were followed for five or more years. Total energy (hazard ratio (HR)=1.58, 95%, confidence interval (CI)= 1.05, 2.38) as well as total (HR = 1.46, 95% CI = 1.05, 2.01), saturated (HR = 1.79,95% CI = 1.05, 3.04), and monounsaturated (HR = 1.65, 95% CI = 1.09,2.49) fat intakes were associated with increased risk, and energy-adjusted bread and cereal consumption (HR = 0.55, 95% CI = 0.33, 0.93) with decreased risk of recurrence. Both total energy (HR = 1.58, 95% CI = 1.03, 2.43) and polyunsaturated fat (HR = 1.84, 95% CI = 1.09, 3.13) intakes were associated with an increased risk of death. All associations between dietary fat and recurrence and survival attenuated following energy adjustment. Oral contraceptive use (HR = 1.28, 95% CI = 1.03, 1.60), lymph node positive status (HR = 2.36, 95% CI = 1.01, 5.49), and tumor stage (HR = 2.22, 95% CI = 1.02, 4.81) were associated with increased risk of recurrence. Tumor stage (HR = 4.96, 95% CI = 1.86, 13.23), lymph node positive status (HR = 3.31, 95% CI = 1.38, 7.95, and estrogen receptor negative status (HR = 2.46, 95% CI = 1.02, 5.94) were associated with increased risk, and arm muscle circumference (HR = 0.27, 95% CI = 0.09, 0.86) and mammographic utilization (HR = 0.77, 95% CI = 0.61, 0.98) with decreased risk of death. Higher levels of energy, fat intakes, and selected patient characteristics (particularly disease stage and anthropometric indicators of adiposity) appear to increase risk of recurrence and/or shortened survival following the diagnosis of breast cancer.     

Recurrences and second primary breast cancers in older women with initial early-stage disease

BACKGROUND: The association between common breast cancer therapies and recurrences and second primary breast cancers in older women is unclear, although older women are less likely to receive common therapies. METHODS: Women aged >or=65 years who were diagnosed with stage I or II breast cancer and who underwent mastectomy or breast-conserving surgery (BCS) from 1990 to 1994 were identified from automated data from 6 healthcare systems and then were followed for 10 years or until breast cancer recurrence, disenrollment, or death. Trained abstractors reviewed medical records to obtain recurrence, tumor, treatment and demographic data. The authors used proportional hazards models to examine predictors of recurrent and second primary breast cancers adjusted for demographic and tumor factors. RESULTS: Of 1837 eligible women, 34% were ages 65 to 69 years, 46% were ages 70 to 79 years, and 20% were aged >or=80 years. In multivariable models that used mastectomy as the reference group, BCS without radiation therapy was associated with an increased risk of any recurrent and second primary breast cancer (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.3), particularly with the subgroup of women with local and regional recurrence (HR, 3.5; 95% CI, 2.0-6.0). Tamoxifen use for <1 year versus >or=5 years exhibited a borderline association with any recurrent or second primary breast cancer (HR, 1.9; 95% CI, 0.9-4.2). CONCLUSIONS: Radiation therapy after BCS and 5 years of tamoxifen use were beneficial in reducing recurrences and second primary breast cancers in older women, regardless of their age or comorbidity burden.     

三阴性对小肿块乳腺癌患者预后的影响

  目的  分析小肿块（直径≤1 cm）乳腺癌患者的临床及病理学特征,了解其生存状态,探讨三阴性对其预后的影响。  方法  收集本院收治的312例直径≤1 cm乳腺癌患者的临床病理学资料,比较三阴性乳腺癌及非三阴性乳腺癌的临床病理学特征、复发转移及生存情况。  结果  312例直径≤1 cm乳腺癌患者纳入研究,三阴组及非三阴组5年DFS分别为81.4%及90.5%（P= 0.038）,5年BCSS分别为84.7%及93.7%（P=0.047）。以淋巴结状态分组比较,淋巴结阴性患者中,三阴组及非三阴组5年DFS分别为82.8%及94.1%（P=0.033）,5年BCSS分别为85.0%及96.1%（P=0.019）。Cox比例风险模型多因素分析显示,淋巴结阳性患者复发转移风险增高（HR=3.721,95%CI:1.743~7.941,P=0.001）,死亡风险亦增高（HR=3.560,95%CI:1.521~8.330,P=0.003）,三阴性患者复发转移风险增高（HR=2.208,95%CI:1.028~4.742,P=0.042）。  结论  淋巴结阳性及三阴性是影响直径≤1 cm乳腺癌患者DFS的独立危险因素,淋巴结阳性是影响BCSS的唯一独立危险因素。淋巴结阴性三阴性乳腺癌组较非三阴组预后差。      

Postdiagnosis weight change is associated with poorer survival in breast cancer survivors: A prospective population‐based patient cohort study

More women are surviving after breast cancer due to early detection and modern treatment strategies. Body weight also influences survival. We aimed to characterize associations between postdiagnosis weight change and prognosis in postmenopausal long‐term breast cancer survivors. We used data from a prospective population‐based patient cohort study (MARIE) conducted in two geographical regions of Germany. Breast cancer patients diagnosed 50 to 74 years of age with an incident invasive breast cancer or in situ tumor were recruited from 2002 to 2005 and followed up until June 2015. Baseline weight was ascertained at an in‐person interview at recruitment and follow‐up weight was ascertained by telephone interview in 2009. Delayed entry Cox proportional hazards regression was used to assess associations between relative weight change and all‐cause mortality, breast cancer mortality, and recurrence‐free survival. In total, 2216 patients were included. Compared to weight maintenance (within 5%), weight loss >10% increased risk of all‐cause mortality (HR 2.50, 95% CI 1.61, 3.88), breast cancer mortality (HR 3.07, 95% CI 1.69, 5.60) and less so of recurrence‐free survival (HR 1.43, 95% CI 0.87, 2.36). Large weight gain of >10% also increased all‐cause mortality (HR 1.64, 95% CI 1.02, 2.62) and breast cancer mortality (HR 2.25, 95% CI 1.25, 4.04). Weight maintenance for up to 5 years in long‐term breast cancer survivors may help improve survival and prognosis. Postdiagnosis fluctuations in body weight of greater than 10% may lead to increased mortality. Survivors should be recommended to avoid large deviations in body weight from diagnosis onwards to maintain health and prolong life.     

Sex differences in survival of cutaneous melanoma are age dependent: an analysis of 7338 patients

This study identified sex differences in clinical presentation and survival for primary cutaneous melanoma without clinical evidence of metastasis at diagnosis from 1976 to 2008 in southern Germany. Melanoma-specific survival curves and estimated survival probabilities were generated using the Kaplan-Meier method. Multivariate survival analyses were carried out using the Cox modeling. Male patients had significantly thicker and more frequently ulcerated tumors and a lower 10-year disease-specific survival (DSS) and recurrence-free survival probability compared with females among patients of 43 years old or younger (DSS: 86.1 vs. 93.2%, P<0.001) and 44-60 years old (DSS: 83.5 vs. 90.1%, P<0.001). The survival advantage of female patients in terms of 10-year DSS and 10-year recurrence-free survival was not observed after an age of 60 years (P=0.21 and 0.51, respectively). Sex was of prognostic importance for DSS and survival after recurrence [hazards ratio (HR): 1.3; 95% confidence interval (CI): 1.1-1.6; P=0.002 and HR: 1.2; 95% CI: 1.0-1.5; P=0.018, respectively]. Stratified by age groups, sex remained of prognostic importance for DSS only in patients of 43 years or younger, and 44-60 years old (HR: 1.5; 95% CI: 1.0-2.1; P=0.03 and HR: 1.4; 95% CI: 1.1-2.0; P=0.02, respectively). Sex is an independent prognostic factor in surviving melanoma. The sex difference in survival with a better outcome for women is confined to melanoma patients of 60 years and younger. In addition, in younger age groups, male patients present with prognostically unfavorable features of primary melanoma. A female survival advantage is also known for other solid tumors such as colon and lung cancer; however, age dependency has not been studied.     

Patients with Recurrent Breast Cancer: Does the Primary Axillary Lymph node Status Predict more Aggressive Tumor Progression?

BACKGROUND: The extent of axillary lymph node involvement represents the foremost important prognostic parameter in primary breast cancer, and, thus, is one of the main determinants for subsequent systemic treatment. Nevertheless, the relevance of the initial axillary lymph node status on survival after disease recurrence is discussed controversially. Persisting prognostic impact after relapse would identify lymph node status as a marker for tumor biology, in contrast to a simply time-dependent phenomenon. METHOD: Retrospective analysis of 813 patients with locoregional or distant recurrence of primary breast cancer, who were primarily diagnosed with their disease at the I. Frauenklinik, Ludwig-Maximilians-University, Munich, and the University Hospital in Berlin-Charlottenburg, Germany, between 1963 and 2000. To be eligible, patients were required to have been treated for resectable breast cancer free of distant disease at the time of primary diagnosis, and must have undergone systematic axillary lymph node dissection. Patients with unknown tumor size or nodal status were excluded from the study. All data were gathered contemporaneously and compared with original patients files, as well as the local cancer registry, ensuring high quality of data. The median observation time was 60 (standard deviation 44) months. RESULTS: At time of primary diagnosis, 273 patients (33.6%) were node-negative, while axillary lymph node metastases were detected in 540 patients (66.4%). In univariate analysis tumor size, axillary lymph node status, histopathological grading, hormone receptor status, as well as peritumoral lymphangiosis and haemangiosis carcinomatosa were significantly correlated with survival after relapse (all, P < 0.0001). Kaplan-Meier analysis estimated the median survival time after relapse in node-negative patients to be 42 months (31-52 months, 95% CI), and 20 months in patients with 1-3 axillary lymph node metastases (16-24 months, 95% CI), compared to 13 months in patients with at least 4 involved axillary nodes (12-15 months, 95% CI). Multivariate logistic regression analysis, allowing for tumor size, axillary lymph node status, histopathological grading, presence of lymphangiosis carcinomatosa, relapse site and disease-free interval confirmed all parameters, except of histopathological grading (P = 0.14), as significant, independent risk factors for cancer associated death. Subgroup analyses, accounting for site of relapse and duration of disease-free interval, confirmed primary lymph node status as independent predictor for cancer-associated death after relapse. CONCLUSION: Lymph node involvement at primary diagnosis of breast cancer patients predicts an unfavorable outcome after first recurrence, independently of the site of relapse and disease-free interval. These observations support the hypothesis that primary lymph node involvement is not a merely time-dependent indicator for tumor progression, but indicates tumors with aggressive biological behavior.     

Cyclin E的表达和乳腺癌的预后的meta分析

背景与目的：多个临床试验分析了cyclin E与乳腺癌预后的关系，但结果并不一致。本研究对已发表的相关临床试验结果进行再分析，从而探讨肿瘤组织的细胞周期素E（cyclin E）的表达水平是否是乳腺癌的预后因素。方法：检索PubMed以及CBMDisc数据库中研究cyclinE表达与乳腺癌预后关系的文献，使用meta分析的方法分析cyclinE是否为乳腺癌的预后因素。结果：共有13篇符合要求的文献，包括患者的总数为2644人。各个研究之间在病例选择、随访时间、辅助治疗、检测方法以及表达水平的判定标准等方面存在明显的差异。合并的单因素及多因素分析结果显示，高cyclinE水平患者的无复发生存率（RFS）的危险比（HR）分别为2．26（95％CI：1．41—3．61）和1．72（95％CI：0．95—3．10）；高cyclinE水平患者的总生存率（OS）／乳腺癌相关生存率（BCSS）的HR分别为2．74（95％CI：2．22-3．39）和2．86（95％CI：1．85-4．41）。在淋巴结阴性的患者中，合并的高cyclinE水平患者OS的HR为3．40（95％CI：2．20-5．26）。结论：cyclin E可能是乳腺癌OS独立的预后因素，但该结论尚需进一步的大规模临床试验加以验证。