| 1. |
- Fernö, Mårten, et al.
(författare)
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Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 1573-7217 .- 0167-6806. ; 59:1, s. 69-76
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Tidskriftsartikel (refereegranskat)abstract
- A Swedish cooperative trial demonstrated that 5 years of adjuvant tamoxifen was more beneficial than 2 years of tamoxifen in the treatment of postmenopausal women with estrogen receptor (ER) positive, early stage, invasive breast cancer. The main aim of the present study was to investigate the importance of progesterone receptor (PgR) and ER concentration levels for patients participating in the trial and still distant recurrence free two years after the primary operation. Subgroup analyses revealed that only patients with ER positive and PgR positive breast cancer had improved distant recurrence free survival (DRFS) by prolonged tamoxifen therapy (p = 0.0016). Patients with ER negative and PgR negative as well as ER positive and PgR negative tumors showed no significant effect of prolonged tamoxifen (p = 0.53 and p = 0.80, respectively). The percentage of ER negative and PgR positive breast cancers was too small (2.2%) for any meaningful subgroup analysis. There was a significant positive trend that the concentration level of PgR (high positive vs. low positive vs. negative) decreased the recurrence rate for those with prolonged therapy. No corresponding pattern was found for the ER content. S-phase fraction did not correlate to the recurrence rate of PgR positive breast cancers. Patients recurring during tamoxifen therapy had receptor negative tumors to a greater extent than those recurring after tamoxifen treatment. In conclusion, prolonged tamoxifen therapy for 5 years instead of 2 years was found to be beneficial for patients with ER positive and PgR positive breast cancer, whereas three extra years of tamoxifen had little or no effect for patients with ER positive but PgR negative tumors as well as for steroid receptor negative patients.
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| 2. |
- Gunnarsson, Cecilia, 1970-, et al.
(författare)
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Amplification of HSD17B1 has prognostic significance in postmenopausal breast cancer
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 108:1, s. 35-41
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Tidskriftsartikel (refereegranskat)abstract
- In situ synthesis of estrogens is believed to be of great importance for the progression of breast cancer. In postmenopausal women most estrogens are synthesized in peripheral hormone-target tissues from circulating precursor steroids, by the enzymes involved in formation of active estrogens. One of the enzymes involved in this process is 17β-hydroxysteroid dehydrogenase (17β-HSD) type 1. This enzyme catalyzes the interconversion of estrone (E1) to the biologically more potent estradiol (E2). The gene coding for 17β-HSD type 1 (HSD17B1) is located at 17q12-21. The aim of this study was to investigate altered gene copy number of HSD17B1 in breast cancer. We used real-time PCR and examined 387 postmenopausal breast tumors for amplification of HSD17B1, and if an increased mRNA level of this enzyme is associated with amplification of the gene. We also investigated whether amplification of HSD17B1 has a prognostic value. There was a significant correlation between gene copy number of HSD17B1 and mRNA expression level (P = 0.00002). ER-positive patients with amplification of HSD17B1 showed lower breast cancer survival than patients without amplification (P = 0.025). Among ER-negative patients there was no significant correlation between increased gene copy number of HSD17B1 and prognosis. Furthermore, we found that amplification of the gene had prognostic significance in multivariate analysis adjusting for other clinicopathological variables. © 2007 Springer Science+Business Media, LLC.
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| 3. |
- Licznerska, Barbara E., et al.
(författare)
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In situ levels of oestrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients
- 2008
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Ingår i: Breast Cancer Research and Treatment. - Berlin : Springer. - 0167-6806 .- 1573-7217. ; 112:1, s. 15-23
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Tidskriftsartikel (refereegranskat)abstract
- Background The risk of developing breast cancer is strongly correlated with the overall exposure to oestrogen and most tumours are more or less dependent on oestrogen for their growth. A great majority of breast cancers occur after menopause when the ovaries have ceased to be functional, yet breast tumours in postmenopausal women maintain high intratumoural oestrogen concentrations, primarily through enzymatic conversion of androgenic precursors. Patients with a hormone dependent tumour generally receive the anti-oestrogen tamoxifen that mediate its anti-tumour effect by competing with oestrogen for binding to the oestrogen-receptor (ER). We therefore propose that the levels of oestrogen producing enzymes may affect the prognosis in postmenopausal breast cancer patients treated with tamoxifen. Methods We measured the mRNA and protein levels of aromatase and sulfatase by real-time PCR (n = 161) and immunohistochemistry (n = 131) in postmenopausal women with breast cancer. Results A significant better recurrence-free survival was detected in patients with weak or high protein expression of stromal aromatase (P = 0.0008), as also demonstrated by a decreased relative risk (RR = 0.50, CI = 0.33–0.76, P = 0.003). When we combined patients with weak and high stromal aromatase and selected only ER-positive patients, the improved prognosis was even more evident (P = 0.0000) and was shown to be a significant prognostic factor in a multivariate Cox-model (HR = 0.15, CI = 0.06–0.39, P = 0.000). The mRNA expression of aromatase and sulfatase, as well as the protein expression of sulfatase revealed no prognostic significance. Conclusion Protein expression of stromal aromatase may serve as a significant prognostic marker in ER-positive patients.
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| 4. |
- Rydén, Lisa, et al.
(författare)
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HER2 status in hormone receptor positive premenopausal primary breast cancer adds prognostic, but not tamoxifen treatment predictive, information
- 2008
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 109:2, s. 351-357
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOverexpression of human epidermal growth factor receptor 2 (HER2) or amplification of its gene is a prognostic factor in primary breast cancer and a predictor for tamoxifen treatment efficacy in oestrogen receptor (ER) positive disease. In the present study we explored a defined cohort of breast cancer patients included in a randomised trial in order to assess prognostic and tamoxifen treatment information yielded by HER2 status.MethodsPremenopausal breast cancer patients with stage II tumours (n = 564) were included and allocated to 2 years of adjuvant tamoxifen treatment versus no adjuvant treatment. ER, progesterone receptor (PR) status and HER2 status was determined by immunohistochemistry using a tissue microarray. HER2 amplification was analysed by fluorescent in situ hybridisation and tumours being amplified and/or HER2 3+ were considered HER2+. HER2 status was evaluable in 83% of the patients and 12.6% were HER2+. In untreated patients, HER2 was a negative prognostic factor in ER+ patients, HR 2.95; 95% CI: 1.61–5.38, p < 0.001, but not in ER- patients, HR 0.67; 95% CI: 0.28–1.61, p = 0.4, and a significant interaction between the two markers was found, p < 0.01. HER2 status was not related to tamoxifen treatment efficacy in ER+ patients (term of interaction p = 0.95). When stratifying for PR status, similar results were achieved.DiscussionHER2+ and ER+ breast cancer constituted a subgroup of tumours with poor prognosis in premenopausal breast cancer, whereas no treatment interaction was found between HER2 status and tamoxifen in ER+ tumours. The poor prognosis in HER2+ and ER+ patients may interfere with the interpretation of HER2 data in non-randomised trials of adjuvant tamoxifen.
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| 5. |
- Sundquist, Marie, et al.
(författare)
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A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer
- 2000
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 63:1, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2–11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.
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| 6. |
- Sundquist, Marie, et al.
(författare)
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Applying the Nottingham Prognostic Index to a Swedish breast cancer population
- 1999
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Ingår i: Breast Cancer Research and Treatment. - 0167-6806 .- 1573-7217. ; 53:1, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess the applicability of histopathological grading according to the protocol of Elston/Ellis and the Nottingham Prognostic Index (NPI) to a defined breast cancer population. The NPI is the sum of the individual scores concerning grade, tumour size, and lymph node status, each weighted according to regression coefficients of a Cox proportional hazard analysis and calculated for each individual breast cancer patient. 630 consecutive patients with invasive breast cancer diagnosed 1988–91 were retrospectively followed up and their tumours reviewed and graded. A Cox proportional hazard analysis was performed. Grade, lymph node status, and tumour size were statistically significant predictors of survival within the follow up period (median 7.2 years). Similar to NPI, a temporary index (Kalmar Prognostic Index, KPI) was derived and normalised to NPI for comparison (KPI(norm)). NPI and KPI(norm) gave similar prognostic power in spite of the differences of the patient populations from which the 2 indices were derived. Patients with NPI 4 or less had 0.66% breast cancer specific mortality during the follow up time. 14% of the patients with NPI 4.1–5 and 32% of those with an index sum 5.1–6 died from breast cancer during this time. Younger patients tended to have higher grade tumours. We advocate the common use of grade and the NPI in order to increase the comparability of groups of patients receiving different therapies.
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