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- Andersson, G., et al.
(författare)
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Stromal progesterone receptor expression and long-term survival in patients with resected periampullary adenocarcinoma
- 2018
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 262-263
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Early trials have reported a beneficial effect from tamoxifen treatment in patients with unresectable pancreatic cancer, in particular in women. However, the presence and prognostic significance of female hormone receptors in pancreatic or other periampullary cancers has not yet been described. Methods: Immunohistochemical screening of normal and malignant pancreatic tissue revealed that the predominantly expressed female hormone receptor was the progesterone receptor (PgR), in particular in the cancer-associated stroma. The impact of PgR expression on overall survival (OS) was further examined on tissue microarrays with primary tumours from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinoma. Results: Median follow-up time was 29.7 (range 1.9–185.1) months. Stromal PgR positivity (PgR+), allover denoted in 31% of the cases, was significantly higher in pancreatobiliary-type than in intestinal-type tumours (38.7% vs 19.0%, p = 0.008), with an equal distribution between sexes. Stromal PgR+ was significantly associated with a prolonged OS in KRAS-mutated tumours, whereas the opposite was seen in KRAS wild-type tumours (p for interaction =0.015). This association was particularly evident in women, with a median OS of 60.5 months for PgR+/KRAS mutated tumours and 9.9 months for PgR+/KRAS wild-type tumours (p for interaction <0.001). PgR expression was not prognostic in male patients. Conclusions: The finding of stromal PgR expression, and its link to clinical outcome in a considerable proportion of pancreatic and other periampullary cancers is novel. The concept of tamoxifen treatment for patients with unresectable disease, in particular elderly women, should be pursued, and PgR and KRAS may be relevant biomarkers for improved patient stratification.
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- Berntsson, J., et al.
(författare)
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Pre-diagnostic anthropometry, sex, and risk of colorectal cancer according to tumor-infiltrating immune cell composition
- 2018
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology. - : Elsevier BV. - 1569-8041. ; 29:Suppl. 8, s. 180-180
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Obesity is a well-established risk factor for colorectal cancer (CRC), but whether this risk differs according to CRC subtype defined by the tumor immune microenvironment has been sparsely described. Herein, we examined the relationship between pre-diagnostic anthropometry and CRC risk according to tumor-infiltrating immune cell composition, with particular reference to potential sex differences. Methods: The density of immune cells expressing PD1, PD-L1 (PD-L1/IC), CD3, CD8, FoxP3, CD20, CD68, CD163, and tumor cells expressing PD-L1 (PD-L1/TC) was assessed by immunohistochemistry in tissue microarrays with tumors from 584 incident CRC cases in the Malmö Diet and Cancer Study (n = 28098). Multivariable Cox regression models, adjusted for age, smoking and alcohol intake, were applied to calculate hazard ratios (HR) for CRC risk according to height, weight, bodyfat %, waist- and hip circumference, waist-hip ratio (WHR), body mass index (BMI), and different immune cell subsets. Results: Obesity, measured as several anthropometric factors, was significantly associated with PD-L1+/TC low, CD8+ high, FoxP3+ low, CD20+ low, and CD163+ low tumors in both sexes, and with PD1+ low tumors in women. A contrasting risk between sexes was seen for PD-L1/IC+ tumors, in that obesity was significantly associated with risk of PD-L1/IC+ high tumors in women (ptrend for weight = 0.008, ptrend for BMI = 0.039), but with risk of PD-L1/IC+ low tumors in men (ptrend for weight = 0.005, ptrend for bodyfat % = 0.003, ptrend for waist <0.001, ptrend for hip = 0.012, ptrend for BMI = 0.001, ptrend for WHR <0.001). Furthermore, obesity was associated with risk of any CD3+ high or low and any CD68+ high or low tumors in both sexes, and with any PD1+ high or low tumors in men. In age and BMI-adjusted survival analysis, PD1+, CD8+, CD20+, and CD68+ high were favorable prognostic factors only in women, and FoxP3+ high only in men. High PD-L1+ and CD3+ expression was prognostic in both sexes. Conclusions: Anthropometric factors may influence the immune landscape of colorectal cancer, possibly in a sex-dependent manner. Thus, obesity and sex may be important factors to take into account when stratifying patients for immunotherapy.
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- Cardoso, F., et al.
(författare)
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Characterization of male breast cancer : Results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program
- 2018
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Ingår i: Annals of Oncology. - : Elsevier BV. - 1569-8041 .- 0923-7534. ; 29:2, s. 405-417
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Tidskriftsartikel (refereegranskat)abstract
- Background: Male breast cancer (BC) is rare, managed by extrapolation from female BC. The International Male BC Program aims to better characterize and manage this disease. We report the results of part I, a retrospective joint analysis of cases diagnosed during a 20-year period. Methods: Patients with follow-up and tumor samples, treated between 1990 and 2010, in 93 centers/9 countries. Samples were centrally analyzed in three laboratories (the United Kingdom, the Netherlands and the United States). Results: Of 1822 patients enrolled, 1483 were analyzed; 63.5% were diagnosed between 2001 and 2010, 57 (5.1%) had metastatic disease (M1). Median age at diagnosis: 68.4 years. Of 1054 M0 cases, 56.2% were node-negative (N0) and 48.5% had T1 tumors; 4% had breast conserving surgery (BCS), 18% sentinel lymph-node biopsy; half received adjuvant radiotherapy; 29.8% (neo)adjuvant chemotherapy and 76.8% adjuvant endocrine therapy (ET), mostly tamoxifen (88.4%). Per central pathology, for M0 tumors: 84.8% ductal invasive carcinomas, 51.5% grade 2; 99.3% estrogen receptor (ER)-positive; 81.9% progesterone receptor (PR)-positive; 96.9% androgen receptor (AR)-positive [ER, PR or AR Allred score ≥ 3]; 61.1% Ki67 expression low (<14% positive cells); using immunohistochemistry (IHC) surrogates, 41.9% were Luminal-A-like, 48.6% Luminal-B-like/HER-2-negative, 8.7% HER-2-positive, 0.3% triple negative. Median follow-up: 8.2 years (0.0-23.8) for all, 7.2 years (0.0-23.2), for M0, 2.6 years (0.0-12.7) for M1 patients. A significant improvement over time was observed in age-corrected BC mortality. BC-specific-mortality was higher for men younger than 50 years. Better overall (OS) and recurrence-free survival (RFS) were observed for highly ER+(P=0.001), highly PR+(P=0.002), highly AR+ disease (P=0.019). There was no association between OS/RFS and HER-2 status, Ki67, IHC subtypes nor grade. Conclusions: Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in > 90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.
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