Ovarian cancer in younger vs older women: a population-based analysis

To compare the clinico-pathologic prognostic factors and survival of younger vs older women diagnosed with epithelial ovarian cancer. Demographic, clinico-pathologic, treatment, and surgery information were obtained from patients with ovarian cancer from the Surveillance, Epidemiology, and End Results Program from 1988 to 2001 and analysed using Kaplan-Meier estimates. Of 28 165 patients, 400 were <30 years (very young), 11 601 were 30-60 (young), and 16 164 were >60 (older) years of age. Of the very young, young, and older patients, 261 (65.3%), 4664 (40.2%), and 3643 (22.5%) had stage I-II disease, respectively (P<0.001). Across all stages, very young women had a significant survival advantage over the young and older groups with 5-year disease-specific survival estimates at 78.8% vs 58.8 and 35.3%, respectively (P<0.001). This survival difference between the age groups persists even after adjusting for race, stage, grade, and surgical treatment. Reproductive age (16-40 years) women with stage I-II epithelial ovarian cancer who received uterine-sparing procedures had similar survivals compared to those who underwent standard surgery (93.3% vs 91.5%, P=0.26). Younger women with epithelial ovarian cancer have a survival advantage compared to older patients.     

Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer

Background: There is limited knowledge about prognosis of selected breast cancer subtypes among very young women.Patients and methods: We explored patterns of recurrence by age according to four immunohistochemically defined tumor subtypes: Luminal A and Luminal B (estrogen receptor positive and/or progesterone receptor positive and either human epidermal growth factor receptor 2 (HER2) positive and/or high Ki-67), HER2-positive (and) endocrine receptor absent and Triple Negative, in 2970 premenopausal patients with pT1-3, pN0-3 and M0 breast cancer.Results: Patients <35 years of age (315, 11%) presented a significantly increased risk of recurrence and death [hazards ratio (HR) = 1.65, 95% confidence interval (CI) 1.30–2.10 and HR = 1.78, 95% CI 1.12–2.85, respectively] when compared with older patients (2655, 89%) with similar characteristics of disease. This was true considering patients with Luminal B [HR = 1.62, 95% CI 1.21–2.18 for disease-free survival (DFS) and HR = 2.09, 95% CI 0.96–4.53 for overall survival (OS)] and with Triple Negative (HR = 2.04, 95% CI 1.11–3.72 for DFS and HR = 2.20, 95% CI 1.10–4.41 for OS) breast cancer, observing the highest risk of recurrence in the younger patients with HER2-positive breast cancer (HR = 2.37, 95% CI 1.12–5.02) when compared with older patients.Conclusions: Very young patients with Triple Negative, Luminal B or HER2-positive breast cancer have a worse prognosis when compared with older patients with similar characteristics of disease.     

Epidemiological study of urinary 6beta-hydroxycortisol to cortisol ratios and breast cancer risk.

The ratio of urinary 6beta-hydroxycortisol:cortisol is a measure of the activity of cytochrome p450 3A4 (CYP3A4). CYP3A4 catalyzes the formation of the genotoxic estrogen, 16alpha-hydroxyestrone. It is also involved in the activation of many other mammary carcinogens, such as the polycyclic aromatic hydrocarbons and heterocyclic amines. We evaluated the association between urinary cortisol ratios and breast cancer risk in a subgroup of women who participated in a population-based case-control study in Shanghai. Overnight urine samples from 246 case-control pairs were assayed for 6beta-hydroxycortisol (6beta-OHC) to cortisol. The urine samples from all of the breast cancer patients were collected before any chemotherapy or radiotherapy. In-person interviews were conducted to obtain comprehensive information on dietary habits, reproductive history, and other lifestyle factors. The median levels of 6beta-OHC:cortisol ratios were 2.61 in cases and 2.16 in controls, a 20.8% difference (P < 0.001). The case-control difference was larger in women over 45 years of age (31.3% difference; P < 0.001) than younger women (6.0%; P = 0.45). After adjusting for confounding variables, the risks of breast cancer were increased from 1.0 (reference) to 1.6 [95% confidence interval (CI), 0.9-3.1], 2.2 (95% CI, 1.1-4.2), and 3.7 (95% CI, 1.9-7.4; P for trend, <0.001) with increasing levels of 6beta-OHC:cortisol ratios. The positive association was more pronounced among older women (>45 years) than among younger women (< or = 45 years). The adjusted odds ratios associated with the highest cortisol ratio were 6.0 (95%CI, 2.2-16.1) among older women and 2.2 (95%CI, 0.8-6.1) among younger women. The association of the 6beta-OHC:cortisol ratio was stronger among older women who had a high body mass index, late age at menopause, and early age at menarche (factors related to high endogenous estrogen exposure) than those who did not have these factors. These findings are consistent with the role of CYP3A4 in estrogen and carcinogen metabolism and suggest that high CYP3A4 activity may be a risk factor for breast cancer risk.     

Microvessel density and p53 overexpression in young women with breast cancer: a case-control study

Several reports have indicated that young women (less than 40 years of age) with breast cancer have a worse prognosis than older women. We performed a case-control study in order to confirm this observation and to determine whether this was attributable to increased microvessel density (MVD) or p53 expression. Twenty-six young women (cases) with stage I-III breast cancer that had adequate paraffin-embedded archival tissue were identified by the Montefiore Medical Center Tumor Registry over a 24-year period. For each case, two or three control subjects at least 40 years of age or older were selected from the registry and matched for nodal status and tumor size. Immunohistochemistry was performed for MVD and p53 overexpression. A Cox proportional hazard model was performed to examine the influence of age, MVD, p53 overexpression, and recognized prognostic factors on disease-free and overall survival. There were 26 cases (median age, 36 years) and 72 controls (median age, 64 years). The groups were well matched for known prognostic variables. There was no significant difference in p53 overexpression or MVD in the cases and controls. In multivariate analysis, the only features associated with an increased risk of recurrence included young age (hazard ratio [HR] = 2.49; 95% confidence interval [CI]: 1.18-5.25; P = 0.02) and positive lymph nodes (HR = 2.44; 95% CI: 1.12-5.30; P = 0.02). We have confirmed previous reports demonstrating a worse prognosis for women younger than 40 years with invasive breast cancer but found no correlation between young age and MVD or p53 overexpression when adjusted for other variables.     

Older women with breast carcinoma are less likely to receive adjuvant chemotherapy: evidence of possible age bias?

BACKGROUND: Older women with breast carcinoma are less likely than younger women to receive adjuvant chemotherapy. The authors hypothesized that after controlling for confounders (i.e., variables related to both age and chemotherapy use) and effect modifiers (i.e., variables that have a significant interaction with age), age would become a less significant factor for predicting adjuvant chemotherapy use. METHODS: Data on 480 women with localized breast carcinoma were entered into the National Comprehensive Cancer Network database at The Ohio State University Medical Center. Women were divided into 3 groups: women age < 50 years (n = 143 [30%]), women ages 50-65 years (n = 216 [45%]), and women age > 65 years (n = 121 [25%]). Chi-square and Wilcoxon rank sum tests were used for univariate analyses of the variables of interest, and logistic regression was used for multivariate analyses. RESULTS: After adjustment for confounders (stage, tumor size, progesterone receptor status, and lymph node involvement) and effect modifiers (namely, estrogen receptor [ER] status), the odds of not receiving chemotherapy for women ages 50-65 years and women age > 65 years with ER-positive breast carcinoma were approximately 6 (odds ratio [OR], 6.4; 95% confidence interval [CI], 3.1-13.3; P < 0.001) and 62 (OR, 62.4; 95% CI, 21.8-178.7; P < 0.001) times greater, respectively, than the odds for women age < 50 years. Women ages 50-65 years with ER-negative breast carcinoma were not significantly different from women age < 50 years with respect to chemotherapy use (OR, 1.9; 95% CI, 0.5-7.3; P = 0.374). However, the odds of not receiving chemotherapy for women age > 65 years with ER-negative breast carcinoma were 7 times (OR, 6.7; 95% CI, 1.5-30.6; P = 0.013) greater than the odds for women age < 50 years. CONCLUSIONS: The results of the current study indicate that based on older age alone, women are less likely to receive adjuvant chemotherapy. In addition, the results suggest that age bias may contribute to undertreatment and lack of accrual of older women into clinical trials.     

The association of plasma DHEA and DHEA sulfate with breast cancer risk in predominantly premenopausal women.

Concentrations of adrenal androgens are positively associated with postmenopausal breast cancer risk; however, results in premenopausal women are conflicting. Therefore, we conducted a prospective nested case-control study within the Nurses' Health Study II cohort to examine the relationship of DHEA and DHEA sulfate (DHEAS) with breast cancer risk in predominantly premenopausal women. Blood samples were collected from 1996 to 1999. The analysis included 317 cases of breast cancer diagnosed after blood collection and before June 1, 2003; for each case, two controls were matched on age, fasting status, time of day and month of blood collection, race/ethnicity, and timing of blood draw within the menstrual cycle. No associations were observed between DHEA or DHEAS levels and breast cancer risk overall [in situ and invasive; DHEA relative risk (RR), top versus bottom quartile, 1.2; 95% confidence interval (95% CI), 0.8-1.8, P(trend) = 0.53; DHEAS RR, 1.3; 95% CI, 0.9-2.0; P(trend) = 0.07]. However, both DHEA and DHEAS were positively associated with estrogen receptor-positive/progesterone receptor-positive breast cancer (DHEA RR, 1.6; 95% CI, 0.9-2.8, P(trend) = 0.09; DHEAS RR, 1.9; 95% CI, 1.1-3.3, P(trend) = 0.02). We observed a significant interaction by age, with an RR for DHEAS of 0.8 (95% CI, 0.4-1.5, P(trend) = 0.62) for women <45 years old and 2.0 (95% CI, 1.2-3.5, P(trend) = 0.003) for women >/=45 years old; results were similar for DHEA. Our results suggest that adrenal androgens are positively associated with breast cancer among predominately premenopausal women, especially for estrogen receptor-positive/progesterone receptor-positive tumors and among women over age 45 years.     

Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease.

BACKGROUND: There is limited knowledge about prognosis, and treatment effects in young women with node-negative disease. PATIENTS AND METHODS: We evaluated biological features, treatment recommendations and prognosis for 841 premenopausal patients with pT1-3, pN0 and M0, operated from 1997 to 2001. RESULTS: Patients below 35 years (101, 12%) were more likely to have tumors > 2 cm (35.6% versus 24.2%, P = 0.002), grade 3 (48.5% versus 31.9%, P = 0.009) and with elevated Ki-67 expression (62.4% versus 50.7%, P = 0.002). At the multivariate analysis a statistically significant difference in disease-free survival (DFS, HR 4.44; 95% CI 2.53 to 7.78, P < 0.0001), risk of distant metastases (DDFS) (HR 3.23; 95% CI 1.32 to 7.94, P = 0.011) and overall survival (OS) (HR 2.89; 95% CI 1.06 to 7.87, P = 0.038) was observed for younger versus older patients and in the subgroup with endocrine responsive tumors (DFS, HR 5.17, 95% CI 2.72-9.83, P = < 0.0001; DDFS, 3.76, 95% CI 1.33-10.6, P = 0.013; OS, 4.71, 95% CI 1.09-20.4, P = 0.039 ). CONCLUSIONS: Compared with less young, very young patients with endocrine responsive and node-negative breast cancer have a worse prognosis. Tailored treatments should be explored in this cohort of patients.     

Receipt of locoregional therapy among young women with breast cancer

Although younger women with breast cancer have the most to gain from receipt of optimal care, few data are available regarding their receipt of locoregional breast cancer treatments. We identified 317,596 women aged 18-64 who were diagnosed with invasive breast cancer at hospitals reporting to the National Cancer Database, a large national cancer registry, during 2004-2008. We used multivariable logistic regression to assess the association of patient age with mastectomy versus breast-conserving surgery (BCS), radiation with BCS, and postmastectomy radiation therapy (PMRT) with varying indications, adjusting for patient, clinical, and facility characteristics. Overall, 4?% of women were 35?years old or younger and 7?% were 36-40?years old. Women ≤age 40 were significantly more likely to have mastectomy than BCS compared with older women (57?% for age ≤35 and 52?% for ages 36-40 vs. 35?% for ages 61-64, adjusted odds ratio [OR] for age ≤35?=?2.03; 95?% confidence interval (CI) 1.93-2.14 and OR for ages 36-40?=?1.76; 95?% CI 1.69-1.84). Younger women were less likely to receive radiation if BCS was performed (69 and 73 vs. 80?%, OR for age ≤35?=?0.69; 95?% CI 0.65-0.74 and OR for ages 36-40?=?0.74; 95?% CI 0.70-0.78). For those who underwent mastectomy, overall rates of PMRT were low, although women ≤age 35 and ages 36-40 (vs. ages 61-64) were more likely to receive PMRT regardless of clinical indications. Our study suggests that young women with breast cancer may not be receiving optimal locoregional therapy. Efforts are needed to confirm these findings, further understand barriers to care, and increase the receipt of appropriate adjuvant radiation therapy among young women to improve their disease-free and overall survival.     

Prognosis of premenopausal breast cancer and childbirth prior to diagnosis.

PURPOSE: The time interval between last childbirth and subsequent breast cancer diagnosis is emerging as an important prognostic factor for premenopausal women. PATIENTS AND METHODS: We studied, prospectively, 750 women diagnosed with primary invasive breast cancer before age 45 years who participated in the population-based Australian Breast Cancer Family Study (ABCFS). RESULTS: Median follow-up time was 4.9 years (range, 0.8 to 10.8 years). Compared with nulliparous women, women who gave birth within 2 years prior to diagnosis were more likely to have axillary node-positive (58% v 41%; P =.01), and estrogen receptor-negative (58% v 39%; P =.005) tumors. The unadjusted hazard ratios for death were 2.3 (95% CI, 1.3 to 3.8; P =.002), 1.7 (95% CI, 1.1 to 2.6; P =.03), and 0.9 (95% CI, 0.6 to 1.5; P =.8) for patients who gave birth less than 2 years, 2 to 5 years, and 5 or more years before diagnosis, respectively. After adjusting for tumor characteristics, these hazard ratios were reduced to 1.9 (95%CI, 1.1 to 3.2; P =.02), 1.3 (95% CI, 0.8 to 2.1; P =.3), and 0.9 (95%CI, 0.5 to 1.4; P =.5). Modeling showed that, compared with nulliparous women, the mortality hazard ratio in parous women was 1.9, decreasing by 8% (95%CI, 4% to 13%; P <.001) for each year between last birth and breast cancer diagnosis. CONCLUSION: Proximity of last childbirth to subsequent breast cancer diagnosis is a predictor of mortality independent of histopathological tumor characteristics. Clinicians should be aware that women diagnosed with breast cancer within a few years following childbirth may have a worse outcome than that suggested solely by the standard histopathological prognostic factors of their cancer.     

Young age is associated with ipsilateral breast tumor recurrence after breast conserving surgery and radiation therapy in patients with HER2-positive/ER-negative subtype

Young breast cancer patients are more likely than old patients to experience ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS). However, the pathological processes underlying this relationship have not been elucidated. We investigated the effect of young age on IBTR in a Korean cohort of women with different molecular subtypes of breast cancer. We analyzed data of 2,102 consecutive breast cancer patients who underwent BCS and post-surgical radiation therapy (RT) at two Korean institutions between 2000 and 2005. Patients were classified as young (≤ 40 years; N = 513) or old (> 40 years; N = 1,589). Breast cancer subtype was determined by estrogen receptor (ER), progesterone receptor (PR), and HER2. Median follow-up duration was 61 months. The 5-year IBTR rate was 3.4% in young patients and 1.1% in old patients (P < 0.001). Univariate analysis indicated that IBTR rate in young patients with luminal A and HER2 subtypes was significantly greater than in old patients with these subtypes (P = 0.015 and P < 0.001, respectively). Multivariate analysis, which used luminal A subtype in old patients as reference, indicated that HER2 subtype in young patients was associated with increased risk of IBTR (hazard ratio, HR = 12.24; 95% CI: 2.54-57.96). Among old patients, HER2 subtype was not associated with increased IBTR. In conclusion, young women had a higher rate of IBTR after BCS and RT than old women. This difference is mainly among women with HER2 subtype. Aggressive local control and adjuvant therapy should be considered for young women with HER2 subtype breast cancer.     

Estrogen receptor genotypes and haplotypes associated with breast cancer risk

Nearly one in eight US women will develop breast cancer in their lifetime. Most breast cancer is not associated with a hereditary syndrome, occurs in postmenopausal women, and is estrogen and progesterone receptor-positive. Estrogen exposure is an epidemiologic risk factor for breast cancer and estrogen is a potent mammary mitogen. We studied single nucleotide polymorphisms (SNPs) in estrogen receptors in 615 healthy subjects and 1011 individuals with histologically confirmed breast cancer, all from New York City. We analyzed 13 SNPs in the progesterone receptor gene (PGR), 17 SNPs in estrogen receptor 1 gene (ESR1), and 8 SNPs in the estrogen receptor 2 gene (ESR2). We observed three common haplotypes in ESR1 that were associated with a decreased risk for breast cancer [odds ratio (OR), approximately O.4; 95% confidence interval (CI), 0.2-0.8; P < 0.01]. Another haplotype was associated with an increased risk of breast cancer (OR, 2.1; 95% CI, 1.2-3.8; P < 0.05). A unique risk haplotype was present in approximately 7% of older Ashkenazi Jewish study subjects (OR, 1.7; 95% CI, 1.2-2.4; P < 0.003). We narrowed the ESR1 risk haplotypes to the promoter region and first exon. We define several other haplotypes in Ashkenazi Jews in both ESR1 and ESR2 that may elevate susceptibility to breast cancer. In contrast, we found no association between any PGR variant or haplotype and breast cancer. Genetic epidemiology study replication and functional assays of the haplotypes should permit a better understanding of the role of steroid receptor genetic variants and breast cancer risk.     

Prognostic correlation of basic fibroblast growth factor and vascular endothelial growth factor in 1307 primary breast cancers

This study was designed to investigate the possible relationship between the protein expression of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) with p53 status, breast cancer prognostic factors, metastatic site, and survival after adjuvant therapy. Basic fibroblast growth factor and VEGF expression were determined by enzyme-linked immunosorbent assays in cytosol specimens obtained from 1307 patients with T1-3 primary breast cancer (789 node-negative, 518 node-positive) diagnosed between 1990 and 1997. The median follow-up time was 70 months. Increased bFGF expression was more frequently found in tumors with low VEGF expression (r = -0.286; P = 0.095). Increased bFGF was associated with smaller tumors (P < 0.001), absence of axillary metastasis (P = 0.003), low S-phase fraction (P < 0.001), and longer recurrence-free survival (RFS; P = 0.0038) and overall survival (OS; P = 0.0316). Vascular endothelial growth factor was a prognostic factor for RFS (P < 0.0001) and OS (P < 0.0001) in univariate and multivariate analyses (RFS: 95% CI, 1.1-1.7; P = 0.036; OS: 95% CI, 1.2-2.2; P = 0.002), whereas bFGF expression was not correlated with RFS or OS. Increased VEGF content was correlated with shorter survival after adjuvant endocrine therapy (RFS, P = 0.0004; OS, P = 0.0009). Patients with estrogen receptor-negative disease were excluded from the analysis. Basic fibroblast growth factor was not a prognostic factor after adjuvant systemic therapy, nor was it related to metastatic site. Expression of VEGF is an independent prognostic factor for patients with primary breast cancer. High bFGF expression was related to good prognostic features and longer survival times, but did not add prognostic information in multivariate analysis. The results might implicate that different angiogenic pathways exist in human breast cancer.     

Young breast-cancer patients have unfavorable prognosis because of biologically aggressive tumors

A retrospective analysis of 418 breast cancer patients was done to investigate the differencies in survival, in clinical and in histopathological variables between the different age groups giving special attention to young women. Three age groups were used, young (age less-than-or-equal-to 40 years), middle-aged (41-50 years) and elderly women (>50 years). The tumours in young women had high mitotic activity (p<0.001), high S phase fraction (p=0.025), dense lymphocyte infiltration (p=0.027), high nuclear variable values (p=0.020-0.042), bilateral disease (p=0.001) and low estrogen receptor content (p=0.013) as compared with other age groups. The prognosis of patients under the age of 40 was more unfavorable than their middle-aged counterparts (p=0.0207). The young women have more rapidly proliferating breast tumours than the middle-aged or the elderly women, and moreover the tumours are often bilateral.     

Prognostic significance of soluble urokinase plasminogen activator receptor in serum and cytosol of tumor tissue from patients with primary breast cancer.

PURPOSE: The aim of the study was to evaluate the prognostic value of soluble urokinase plasminogen activator receptor (suPAR) in preoperatively obtained sera samples (s-suPAR) from breast cancer patients. EXPERIMENTAL DESIGN: suPAR levels were determined by the use of a kinetic ELISA in sera from 274 breast cancer patients and in tumor cytosols (c-suPAR) from 188 of these patients. In addition, s-suPAR levels were analyzed in 174 female blood donors. RESULTS: The mean s-suPAR level was 3.8 ng/ml (range, 1.6-9.2 ng/ml) in the patients and 3 ng/ml (range, 1.3-6.4 ng/ml) in the donors. The mean c-suPAR level was 0.55 ng/mg protein (range, 0.07-2.83 ng/mg protein). A weak but significant linear association was found between s-suPAR and age in the donors; thus, all of the s-suPAR levels were adjusted for this age dependency (aa-s-suPAR). The aa-s-suPAR levels were significantly increased in the patients as compared with the donors (P < 0.0001). No difference was found in aa-s-suPAR levels between the lymph node-positive and -negative patients (P = 0.27), and no correlation was seen between aa-s-suPAR and c-suPAR (sigma = 0.08; P = 0.71). During the follow-up period (5.9 years) 77 patients experienced a relapse and 69 died. aa-s-suPAR as a continuous variable was significantly associated with relapse-free survival [hazard ratio (HR), 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.003] and overall survival (HR, 1.6; 95% CI, 1.2-2.0; P < 0.0001). In multivariate Cox analysis including the classical prognostic parameters in breast cancer, continuous aa-s-suPAR was significantly associated with both relapse-free survival (HR, 1.4; 95% CI, 1.1-1.7; P = 0.001) and overall survival (HR, 1.4; 95% CI, 1.1-1.8; P = 0.002). In these analyses positive lymph nodes, tumor size >2 cm, and negative estrogen receptor content were also significantly associated with patient outcome. CONCLUSION: This study shows that high preoperative aa-s-suPAR levels are significantly associated with poor outcome for breast cancer patients independent of lymph node status, tumor size, and estrogen receptor status.     

Patterns of breast carcinoma treatment in older women: patient preference and clinical and physical influences

BACKGROUND: Older women have high rates of breast carcinoma, and there are substantial variations in the patterns of care for this population group. METHODS: The authors studied 718 breast carcinoma patients age 67 years and older who were diagnosed with localized disease between 1995 and 1997 from 29 hospitals in 5 regions. Data were collected from patients, charts, and surgeons. Logistic regression analysis was used to evaluate determinants of treatment. RESULTS: Women who were concerned about body image were 1.8 times more likely (95% confidence interval [95% CI], 1.1-2.8) to receive breast conservation surgery and radiotherapy than women without this preference, controlling for other factors. In contrast, women who preferred receiving no therapy beyond surgery were 3.9 times more likely (95% CI, 2.9-6.1) to undergo mastectomy than other women, after considering other factors. Radiotherapy was omitted after breast conservation 3.4 times more often (95% CI, 2.0-5.6) among women age 80 years and older than among women ages 67-79 years, controlling for covariates. Black women tended to have radiotherapy omitted after breast conservation surgery 2.0 times more often (95% CI, 0.9-4.4) than white women (P = 0.09). Women age 80 years and older also were 70% less likely (odds ratio = 0.3; 95% CI, 0.1-0.8) to receive chemotherapy than women ages 67-79 years, controlling for health, functional status, and other covariates. CONCLUSIONS: After considering other factors, patient preferences and age were found to be associated with breast carcinoma treatment patterns in older women. Further research and training are needed to provide care for the growing population of older women that is both clinically appropriate and consonant with a woman's preferences.     

Risk factors by molecular subtypes of breast cancer across a population-based study of women 56 years or younger

Differences in incidence, prognosis, and treatment response suggest gene expression patterns may discern breast cancer subtypes with unique risk factor profiles; however, previous results were based predominantly on older women. In this study, we examined similar relationships in women ≤ 56 years, classified by immunohistochemical staining for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 for 890 breast cancer cases and 3,432 frequency-matched population-based controls. Odds ratios (OR) and 95% confidence intervals (CI) for tumor subtypes were calculated using multivariate polytomous regression models. A total of 455 (51.1%) tumors were considered luminal A, 72 (8.1%) luminal B, 117 (13.1%) non-luminal HER-2/neu+, and 246 (27.6%) triple negative. Triple negative tumors were associated with breast feeding duration (per 6 months: OR = 0.76, 95% CI 0.64-0.90). Among premenopausal women, increasing body size was more strongly associated with luminal B (OR = 1.73, 95% CI 1.07-2.77) and triple negative tumors (OR = 1.67, 95% CI 1.22-2.28). A history of benign breast disease was associated only with increased risk of luminal A tumors (OR = 1.89, 95% CI 1.43-2.50). A family history of breast cancer was a risk factor for luminal A tumors (OR = 1.93, 95% CI 1.38-2.70) regardless of age, and triple negative tumors with higher risks for women <45 (OR = 5.02, 95% CI 2.82-8.92; P for age interaction = 0.005). We found that little-to-no breastfeeding and high BMI were associated with increased risk of triple negative breast cancer. That some risk factors differ by molecular subtypes suggests etiologic heterogeneity in breast carcinogenesis among young women.     

Mutations in the p53 tumor suppressor gene and early onset breast cancer

Among breast cancer patients p53 gene mutation is associated with a poor prognosis. Young women with breast cancer are more likely than older women to have a poor prognosis, but whether p53 gene mutation plays a role in breast cancer in young women is not clear. This study identified 199 breast cancer patients and tested the hypothesis that p53 gene mutation was associated with early onset breast cancer. Patients with p53 gene mutations were 3-times more likely to have an early onset breast cancer (age < or = 40 years at diagnosis) than those without p53 mutations (OR = 3.05, 95% CI = 1.10-8.45). Patients with both missense and silent mutations were 7-times more likely to have a diagnosis of early onset breast cancer (OR = 7.56, 95% CI = 2.22-25.8). Patients with mutations in exon 8 of the p53 gene were 6-times more likely to be diagnosed with early onset breast cancer (OR = 6.48, 95% CI = 1.37-30.6). These findings suggest that p53 gene mutation may hasten the onset of female breast cancer.     

Poorer survival of elderly patients with ovarian cancer: a population-based study

OBJECTIVE: To compare ovarian cancer survival in elderly and young patients. MATERIAL AND METHODS: Using the Geneva Cancer Registry, we identify women diagnosed with primary ovarian cancer between 1980 and 1998. We compared tumors characteristics, treatment patterns of young patients (70 years) by logistic regression. To evaluate the effect of age on prognosis, we compared disease specific survival by Cox proportional hazard analysis, taking into account other prognostic factors. RESULTS: This study included 285 patient aged 70 years and 451相似文献   

青年女性乳腺癌预后因素分析

目的 :探讨 <30岁青年乳腺癌的PCNA和p5 3蛋白表达的意义及与临床各指标和预后的关系。方法 :采用免疫组化S P法对 6 6例 <30岁的青年乳腺癌进行检测 ,用有关统计学方法结合随访资料进行分析。结果 :<30岁青年乳腺癌的PCNA阳性率为 6 3 6 % ,p5 3表达率为 4 3 9% ;PCNA蛋白表达阳性与月经初朝年龄 (P =0 0 2 8)、临床分期 (P =0 0 16 )、核组织分级 (P <0 0 5 )、腋淋巴结转移 (P<0 0 0 0 1)、雌孕激素受体 (P <0 0 1)及预后 (P <0 0 1)有密切关系 ;p5 3蛋白表达仅与核组织分级 (P=0 .0 38)、腋淋巴结转移 (P =0 0 18)及预后 (P <0 0 1)有关。结论 :1)PCNA可以反映青年乳腺癌细胞的增殖活性 ,并与预后有关。 2 )p5 3为预测青年乳腺癌预后的一个有价值的客观标记物。 3) <30岁青年乳腺癌细胞增殖活性强、预后差 ,其细胞增殖活性可能与激素水平有关。     

Should all BRCA1 mutation carriers with stage I breast cancer receive chemotherapy?

To estimate the 15-year survival following a diagnosis of stage I breast cancer among women who carry a BRCA1 mutation and to determine predictors of mortality, including the use of chemotherapy. Patients were 379 women with stage I breast cancer for whom a BRCA1 mutation had been identified, in herself or in a close family member. Patients were followed for up to 15 years from the initial diagnosis of breast cancer. Survival rates were estimated for women by age, tumor size (≤1 cm; >1 cm), ER status (±), and by chemotherapy (yes/no). 42 women died of breast cancer in the follow-up period (11.2 %). Survival rates were similar for women with cancers of size 0–1.0 cm and size 1.1–2.0 cm. Of the 267 women in the study who used chemotherapy, 21 had died (7.9 %) compared to 21 deaths among 112 women who did not receive chemotherapy (18.8 %; p = 0.002). The 15-year survival was 89.4 % for women who received chemotherapy and was 73.1 % for women who did not receive chemotherapy (p = 0.08; log rank). The adjusted hazard ratio for death following a diagnosis of stage I breast cancer associated with chemotherapy was 0.53 (95 % CI 0.28–1.07; p value 0.06) after adjusting for age of diagnosis, tumor size, and estrogen receptor status. This was statistically significant only among women with ER-negative breast cancers (HR = 0.28; 95 % CI 0.10–0.79; p = 0.02). BRCA1 positive women who are treated for stage I breast cancer with chemotherapy have better survival than those who do not receive chemotherapy. The difference cannot be explained by other prognostic factors. All women with invasive breast cancer and a BRCA1 mutation should be considered to be candidates for chemotherapy.