The role of antiestrogen treatment of postmenopausal breast cancer patients with high risk of recurrent disease is evaluated in a nationwide, prospective trial conducted by the Danish Breast Cancer Cooperative Group (DBCG). After total mastectomy and postoperative radiotherapy (RT), 840 patients were randomized to treatment with tamoxifen (RT + TAM) for one year, and 824 were randomized to no further therapy (RT). The recurrenceree survival (RFS) after ten years of lifeable analysis is 31% in the RT + TAM treated group, and 28% in the RT group (p = 0.01). Survival is 38% and 34% in the two treatment groups, respectively (p = 0.04). The data were further analyzed with respect to prognostic factors such as age, number of positive nodes, tumour size, and degree of anaplasia. Survival is prolonged in nearly all subgroups of patients treated with RT + TAM. However, the prolongation is only significant in patients with four or more positive nodes, with tumours of less than 5 centimeters or with tumours of anaplasia grade II. Estrogen (ER) and progesterone receptor (PgR) concentrations were measured in tumours from 309 and 219 patients, respectively. Only patients with ER and PgR values above 100 fmol/mg cytosol protein seemed to have a prolongation of survival. In conclusion, a modest survival benefit is achieved with one year of adjuvant tamoxifen treatment. Nevertheless, this is the first example of a systemic treatment approach being able to change the fatal course of breast cancer in postmenopausal patients. By means of endocrine therapy, and in the context of a new randomized trial, the DBCG will try to improve the survival in these patients even further.
To examine how breast cancers found by mammographic screening differ from those found outside screening.
Comparative cohort study.
Turku, southwestern Finland.
126 women aged 40-74 years with breast cancer detected during the first round of mammographic screening in 1987-90 and 125 women within the same age range with breast cancer detected outside screening during the same period.
Primary tumour size, axillary nodal status, histological features, oestrogen and progesterone receptor concentrations, ploidy, and S phase fraction.
Compared with the controls women with cancers detected by screening had a smaller primary tumour (57 (46%) screened v 11 (10%) controls had tumours less than or equal to 11 mm in diameter, p less than 0.0001), and less often had axillary nodal metastases (104 (83%) screened v 71 (57%) controls node negative, p less than 0.0001). After adjustment for the smaller size of the primary tumour compared with control cancers, those cancers detected by screening were less likely to have axillary nodal metastases (odds ratio 0.44, 95% confidence interval 0.23 to 0.84), poor histological differentiation (0.20, 0.08 to 0.49), high mitotic counts (0.38, 0.15 to 0.97), tumour necrosis (0.45, 0.22 to 0.93) or to be of the ductal histological type (0.46, 0.22 to 0.95). They had low oestrogen receptor (0.29, 0.12 to 0.70) and progesterone receptor (0.35, 0.17 to 0.92) concentrations less often and had smaller S phase fractions (0.72, 0.55 to 0.96) than control cancers.
Even after adjustment for the smaller size of screen detected breast cancers, their histological and cytometric features suggest low malignant potential. They may also be less likely to metastasise to axillary lymph nodes than cancers found outside screening.
Cites: Br J Cancer. 1991 Sep;64(3):588-921911203
Cites: Lancet. 1990 Feb 3;335(8684):241-61967717
Cites: Cytometry. 1989 Jul;10(4):410-62766887
Cites: Lancet. 1985 Apr 13;1(8433):829-322858707
Cites: Natl Cancer Inst Monogr. 1985 May;67:65-744047153
BACKGROUND: Alcohol intake has been reported to be positively associated with an increased risk of postmenopausal breast cancer; however, the association with the estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors remains unclear. METHODS: Self-reported data on alcohol consumption were collected in 1987 and 1997 from 51,847 postmenopausal women in the population-based Swedish Mammography Cohort. Through June 30, 2004, 1188 invasive breast cancer case patients with known ER and PR status were identified during an average 8.3-year follow-up. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of breast cancer, adjusting for age; family history of breast cancer; body mass index; height; parity; age at menarche, first birth, and menopause; education level; use of postmenopausal hormones; and diet. Heterogeneity among groups was evaluated using the Wald test. All statistical tests were two-sided. RESULTS: Alcohol consumption was associated with an increased risk for the development of ER-positive (+) tumors, irrespective of PR status (highest intake [> or = 10 g of alcohol per day] versus nondrinkers, multivariable RR = 1.35, 95% confidence interval [CI] = 1.02 to 1.80; Ptrend
Comment In: J Natl Cancer Inst. 2005 Nov 2;97(21):1563-416264173
The extent of apoptosis and the expression of Bcl-2 was investigated in tumor samples from 165 women who underwent surgery for primary breast carcinoma between 1989 and 1990 in South-East Sweden. Apoptosis was assessed by a DNA fragmentation assay for flow cytometry. Bcl-2 protein expression was analyzed with immunocytochemistry. Bcl-2 immunoreactivity correlated with estrogen receptor (ER) and progesterone receptor (PgR) positivity and was inversely correlated with p53 accumulation. Apoptosis increased with patient age and a high degree of apoptosis was negatively associated with Bcl-2 immunostaining. Apoptosis showed no significant correlation with any of the other variables studied, including prognosis. The group with Bcl-2-positive tumors tended to have a lower risk of distant recurrence than others, but the association of Bcl-2 with recurrence was different in groups divided by ER and PgR status. Whereas Bcl-2 positivity indicated a low recurrence rate among PgR-negative patients, in the PgR-positive group, those with Bcl-2-positive tumors showed a non significantly higher recurrence rate than Bcl-2-negative cases. In the PgR-positive group, Bcl-2-positive tumors also appeared more frequently to be lymph node positive and DNA aneuploid. The results suggest that hormone receptor status is of importance for the prognostic role of Bcl-2. Likewise, patient age merits consideration when apoptosis is studied in human cancer.
We investigated the association between the risk of locoregional recurrence (LRR) and biological subtypes defined by hormonal receptors (HR) and HER-2 status in women with invasive breast cancer (BC). A total of 618 newly diagnosed BC patients were identified from a cancer registry within a single institution with standardized methods of tumor assessment for estrogen receptor (ER), progesterone receptor (PR), and HER-2. Patients were stratified based on surgical treatment, breast-conserving therapy (BCT) versus modified radical mastectomy (MRM), as well as biological subtypes: HR+/HER-2- (ER-positive or PR-positive, HER-2-negative), HR+/HER-2+ (ER-positive or PR-positive, HER-2-positive), HR-/HER-2+ (ER-negative and PR-negative, HER-2-positive) and TN (ER-negative, PR-negative and HER-2-negative). The association between clinicopathological factors, biological subtype and LRR was evaluated with univariate and multivariate Cox analysis. With a median follow-up of 4.8 years, the rate of LRR was 7.5%. On multivariate analysis, TN, tumor size =2 cm and lymph node (LN) positivity were associated with increased risk of LRR (P = 0.023, P = 0.048, and P = 0.0034, respectively). In BCT group, HR-/HER-2+ and LN positivity were associated with increased risk of LRR (HR 11.13; 95% CI 2.78-44.53; P = 0.0007 and HR 5.40; 95% CI 1.67-17.43; P = 0.0048, respectively). In MRM group, TN subtype and LN positivity were associated with increased risk of LRR (HR 4.72; 95% CI 1.53-14.52; P = 0.0069 and HR 3.23; 95% CI 1.44-7.29; P = 0.0047, respectively). Compared to HR+/HER-2-, HR-/HER-2+ treated by BCT and TN treated by MRM showed a significant decrease of 5-year LRR free survival (P = 0.0002 and P = 0.002, respectively). Tumor profiling using ER, PR, and HER-2 biomarkers is a promising tool to identify patients at high risk of LRR based on surgical treatment. Our findings suggest a different follow-up and locoregional treatment for patients with HR-/HER-2+ and TN subtypes.
Long-term exposure to oestrogens is a well-recognised risk factor for breast cancer, whereas little is known about the influence of polymorphisms of genes involved in oestrogen biosynthesis and metabolism. A candidate, containing a single bp polymorphism, T-->C, (designated, A2 allele), might be the CYP17 gene, which codes for an enzyme involved in oestrogen synthesis. This polymorphism creates an additional Sp1-type promoter site (CCACC box), which has been shown to be associated with increased serum oestrogen levels. We performed a case-control study, to evaluate association of the CYP17 gene polymorphism with risk of breast cancer in young women (younger than 37 years). We found a statistically significant increased risk in carriers of at least 1 A2 allele [odds ratio (OR), 2.0; 95% confidence interval (CI), 1.1-3.5, p = 0.027], and a trend toward a gene-dose effect illustrated by a slightly higher risk for A2-homozygous subjects (OR, 2.8) than for heterozygous women (OR, 1. 9). Furthermore, when we investigated the CYP17 genotype in relation to tumour characteristics, breast cancer patients with 1 or 2 A2 alleles tended to have lower oestrogen receptor levels (risk ratio, 0.70; CI, 0.41-1.2, p = 0.44). Our findings suggest that CYP17 gene polymorphism influences breast carcinogenesis in young women. Int. J. Cancer (Pred. Oncol.) 84:350-353, 1999.
Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years' follow-up.
Molecular profiles of asynchronous breast cancer metastases are of clinical relevance to individual patients' treatment, whereas the role of profiles in synchronous lymph node metastases is not defined. The present study aimed to assess individual biomarkers and molecular subtypes according to the St Gallen classification in primary breast tumours, synchronous lymph node metastases and asynchronous relapses and relate the results to 10-year breast cancer mortality (BCM). Tissue microarrays were constructed from archived tissue blocks of primary tumours (N = 524), synchronous lymph node metastases (N = 147) and asynchronous relapses (N = 36). The samples were evaluated by two independent pathologists according to oestrogen receptor (ER), progesterone receptor (PR), Ki67 and human epidermal growth factor receptor 2 (HER2) by immunohistochemistry and in situ hybridisation. The expression of biomarkers and molecular subtypes in the primary tumour was compared with that in the synchronous lymph node metastases and relapses, and related to 10-year BCM. Discordances were found between primary tumours and relapses (ER: p = 0.006, PR: p = 0.04, Ki67: p = 0.02, HER2: p = 0.02, St Gallen subtypes: p = 0.07) but not between primary tumours and metastatic lymph node. Prognostic information was gained by the molecular subtype classification in primary tumours and nodal metastases; triple negative subtype had the highest BCM compared with the luminal A subtype (primary tumours: HR 4.0; 95 % CI 2.0-8.2, p
Bovine cytosol estrogen (ERC) and progesterone receptor (PRC) concentrations were measured simultaneously in various regions of the uterus and in ovarian stromal tissue in cows with cystic ovarian disease (follicular cysts), and the concentrations compared with those in animals with normal cycles. In cystic ovarian disease, ERC concentrations in endometrium (550 fmol/mg cytosol protein (c.p.)) and in myometrium (405) were significantly higher than in control animals. Very high PRC contents were measured in the endometrium (3115) and myometrium (2761) of cows with cystic ovarian disease. In control animals, PRC concentrations in the endometrium and myometrium were significantly lower than in diseased animals. No statistical differences were observed in ERC or PRC contents between the endometrium and the myometrium in cows with cystic ovarian disease. ERC and PRC concentrations in the uterine cervix and ovaries were low compared to those detected in the uterus. Bovine serum estradiol-17 beta concentrations were higher (p
The purpose was to analyse the characteristics, treatment, recurrences and survival of very young women with breast cancer.
212 female breast cancer patients =35 years old were treated during 1997-2007. The median follow-up time was 78 months.
117 patients had lymph node metastases and 14 distant metastases at diagnosis. 81 (38%) tumours were hormone receptor negative and 130 (65%) grade 3. HER2 positivity was seen in 47 (34%) and triple negativity in 35 (26%) of the 137 tumours with known HER2 status. 140 women were treated with mastectomy and 68 with breast conserving surgery. 163 patients received postoperative radiotherapy, 175 adjuvant chemotherapy, 95 endocrine therapy and 18 trastuzumab. 63 patients experienced a recurrence, of which 20 had only a locoregional recurrence. 10 (15%) of the women with breast conserving surgery experienced ipsilateral breast tumour recurrence while ipsilateral thoracic wall recurrence was seen in 8 patients (6%) after mastectomy. Seven of these eight patients did not receive postmastectomy radiotherapy. DFI was shorter in patients with hormone receptor positive tumours. At the end of follow-up 44 women had died. The 5-year OS was 80%.
The 5-year OS for young women has become better but is still lower than for all breast cancer patients. DFI was shorter in patients with hormone receptor positive disease. Locoregional recurrences were seen more often after breast conserving surgery.
Compared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.
Distant disease-free survival (DDFS) was studied in 504 women aged