When ipsilateral multifocal primary breast cancer (IMBC) is detected, standard routine is to evaluate the largest tumor with immunohistochemistry (IHC). As all foci are not routinely characterized, ...many patients may not receive optimal adjuvant treatment. Here, we assess the clinical relevance of examining at least two foci present in patients with IMBC.
Patients diagnosed and treated for IMBC at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2012 and 2017 were screened. In total, 180 patients with ≥ 2 invasive foci (183 specimens) were assessed with IHC and included in this study. Expression of the estrogen (ER) and progesterone (PR) receptors, Ki67, HER2, and tumor grade were used to determine the molecular surrogate subtypes and discordance among the foci was recorded. An additional multidisciplinary team board was then held to re-assess whether treatment recommendations changed due to discordances in molecular surrogate subtype between the different foci.
Discordance in ER, PR, HER2, and Ki67 was found in 2.7%, 19.1%, 7.7%, and 16.9% of invasive foci, respectively. Discordance in the molecular surrogate subtypes was found in 48 of 180 (26.7%) patients, which resulted in therapy changes for 11 patients (6.1%). These patients received additional endocrine therapy (n = 2), chemotherapy (n = 3), and combined chemotherapy and trastuzumab (n = 6).
Taken together, when assessing at least two tumor foci with IHC, regardless of shared morphology or tumor grade between the different foci, 6.1% of patients with IMBC were recommended additional adjuvant treatment. A pathologic assessment using IHC of all foci is therefore recommended to assist in individualized treatment decision making.
Abstract Purpose In the last 25 years new treatment options in breast cancer have evolved. We wanted to determine whether the survival of; patients with metastatic breast cancer have improved during ...this period. Methods Patients consecutively diagnosed with disseminated breast cancer 1985–2014 in the County of Kalmar, Sweden, were identified and followed to 2016. Survival was calculated for each successive 5 year interval. Separate analyses were performed for pts with ER and/or PR and HER2 positive tumours resp. Results Median survival of the 784 patients increased successively from 13 to 33 months. Five year survival increased from 10 to 27%. Patients with high grade primary tumours had the shortest post recurrence survival time but their median survival increased significantly by time from 12 to 30 months, 3 year survival from 16 to 38% and 5 year from 5 to 20%. Median survival for patients with grade 2 tumours was 2 years and did not improve. Only 47 patients had grade 1 tumours and their median survival of 4 years did not change. Median survival for HER2 positive patients treated before the introduction of trastuzumab in year 2000 was 14 months and after 2000 29 months, 5 year survival improved from 2 to 31%. Conclusions Survival in metastatic breast cancer improved 1985–2016. For the first time a significant increase in survival time for patients with metastasis from fast-growing grade 3 tumours was seen. The most striking improvement was achieved in the HER2 positive subset.
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.
Clinical decision-making for patients with breast cancer (BC) is still primarily based on biomarker characteristics of the primary tumor, together with the evaluation of synchronous axillary lymph ...node metastasis (LNM). In this study, we investigated the prevalence of discordance in the biomarkers and surrogate subtyping between the primary BC and the LNM, and whether subsequent changes would have altered clinical treatment recommendations. In this retrospective study, 94 patients treated for unifocal primary BC and synchronous LNM at Sahlgrenska UniversityHospital during 2018 were included. Estrogen (ER) and progesterone (PR) receptor, Ki67, and HER2 status were assessed in the primary tumor and LNM using immunohistochemistry. Discordances between the primary tumor and the LNM were analyzed for each individual biomarker and surrogate subtyping. The concordance between the primary tumor and the LNM for ER, PR, Ki67, and HER2 status was 98.9%, 89.4%, 72.3%, and 95.8%, respectively. Discordance in surrogate subtyping was found in 28.7% of the tumors and matched LNMs, the majority (81.5%) of which changed to a more favorable subtype in the LNM; most commonly from Luminal B to Luminal A (48.6%). No changes in surrogate subtyping were detected where ER or HER2 status changed from negativity in the BC to positivity in the LNM, thereby showing no additional value in performing immunohistochemistry on the LNM from a treatment decision-making perspective. However, large studies need to be performed that test both the primary BCs and synchronous LNMs for more accurate diagnostics.
Equine insect bite hypersensitivity (IBH) is a pruritic skin allergy caused primarily by biting midges, Culicoides spp. IBH susceptibility has polygenic inheritance and occurs at high frequencies in ...several horse breeds worldwide, causing increased costs and reduced welfare of affected horses. The aim of this study was to identify and validate single nucleotide polymorphisms (SNPs) associated with equine IBH susceptibility. After quality control, 33,523 SNPs were included in a Bayesian genome‐wide association study on 177 affected and 178 unaffected Icelandic horses. We report associated regions in E. caballus (ECA) 1, 3, 15 and 18, overlapping with known IBH QTLs in horses, and novel regions containing several genes, together explaining 11.46% of the total genetic variance. For validation, three SNPs on ECA 1 and ECA X (explaining the largest percentage of genetic variance) within 1‐mb genomic windows for IBH were genotyped in an independent population of 280 Exmoor ponies. The associated genomic region (152–153 mb) on ECA 1 was confirmed in Exmoor ponies and contains the AQR gene involved in splicing processes and a long non‐coding RNA. This study confirms the polygenic nature of IBH susceptibility and suggests a role of transcriptional regulatory mechanisms (e.g., alternative splicing) for IBH predisposition in these horse breeds.
Background: Risk of developing breast cancer increases with short breastfeeding and the use of hormones. The prognosis of breast cancer is better if the tumours are hormone receptor positive. Since ...breast feeding affects estrogen and progesterone receptors, we wanted to investigate how such reproductive factors as breastfeeding and the use of hormones interact with known prognostic markers and specific tumour characteristics in women with breast cancer. Materials and Methods: A total of 250 women treated for breast cancer from a larger cohort completed a questionnaire on breastfeeding, number and age at births and use of hormones. A logistic regression analysis was made to search for connections between known prognostic markers on the one hand (type of cancer, grade, tumor size, estrogen receptor and progesterone receptor, lymphovascular invasion and DNA-ploidy) and reproductive data, breastfeeding, and hormone use on the other. Results and Conclusions: Hormone use, but not breastfeeding, was significantly associated, also on multivariate analysis, with the prognostic variable lymphovascular invasion, connected to a worse prognosis. No other hormone use or breast feeding correlations with prognostic variables were found.
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