Background: The subtype of claudin-low breast cancer can be reliably determined only by gene-expression profiling. Attempts have been made to develop immunohistochemical surrogates, which nearly always focus on membranous claudin expression. Methods: We assessed the immunohistochemical expression of both membranous and cytoplasmic claudins 3, 4 and 7 in a series of 197 non-metastatic breast cancers, enriched with triple-negative breast cancers (TNBCs; 60%). The expression of epithelial-to-mesenchymal transition-regulating transcription factors Sip1, Zeb1 and vimentin had previously been determined in the same material.

ObjectivesAlthough novel early breast cancer prognostic factors are being continuously discovered, only rare factors predicting survival in metastatic breast cancer have been validated. The prognostic role of early breast cancer prognostic factors in metastatic disease also remains mostly unclear.Design and settingProspective cohort study in a Finnish University Hospital.Participants and outcomes594 women with early breast cancer were originally followed. Sixty-one of these patients developed distant metastases during the follow-up, and their primary breast cancer properties, such as tumour size, nodal status, oestrogen receptor (ER) and progesterone receptor expression, grade, proliferation rate, histopathological subtype and breast cancer subtype were analysed as potential prognostic factors for metastatic disease.ResultsIn multivariate analysis, the presence of lymph node metastases at the time of early breast cancer surgery (HR, 2.17; 95% CI, 1.09–4.31; p=0.027) and ER status (negative vs positive, HR, 2.16; 95% CI, 1.14–4.10; p=0.018) were significant predictors of survival in metastatic disease.ConclusionsThese results confirm ER status as a primary prognostic factor in metastatic breast cancer. Furthermore, it also suggests that the presence of initial lymph node metastases could serve as a prognostic factor in recurrent breast cancer.

While breast cancer prognoses are generally good, different molecular subtypes are known to have varying outcomes. Previous studies using breast cancer registries have suggested that high parity may be an adverse prognostic factor in luminal breast cancer, but breast cancer subtype definitions have varied and there have been few prospective studies. We therefore collected prospective data from patients diagnosed with early breast cancer at a single institution and followed them for a median of 8.5 years. All patients (N = 594) were treated according to Finnish national guidelines using modern treatment modalities in a Finnish university hospital. Clinicopathological surrogates of the intrinsic breast cancer subtypes were updated to match European Society for Medical Oncology 2015 Early Breast Cancer Clinical Practice Guidelines. The overall 10-year breast cancer-specific survival (BCSS) was 91.4%, with the longest 10-year BCSS observed in luminal Alike cancers (97.9%) and the worst in luminal B-like (HER2 positive) cancers (80.6%). Parity of ≥ 5 deliveries was also associated with poor BCSS (univariate P = 0.0020). However, when the subtypes were assessed separately in a multivariate analysis that included tumor size and nodal status, high parity remained significant only in luminal B-like (HER2 negative) cancers (HR = 2.63; 95% confidence interval = 1.04-6.62; P = 0.040). Our results suggest excellent overall 10-year BCSS but indicate that high parity is an adverse prognostic factor in luminal B-like (HER2 negative) breast cancers.

Background/Aim: The aim of the study was to investigate the prognostic role of androgen receptor (AR), mineralocorticoid receptor (MR) and glucocorticoid receptor β (GRβ) expression in HER-2 negative breast cancer patients. Materials and Methods: The study population (n=152) was enriched with triple-negative breast cancers (TNBC) (n=96; 63.2%). The median follow-up time was 100 months. AR, MR and GRβ immunocytochemical staining was compared with that of epithelial-mesenchymal transition (EMT) markers (vimentin, SIP1, ZEB1). Results: High expression of cytoplasmic MR was associated with dismal local relapse-free survival (RR=13.923; 95%CI=1.071-181.045; p=0.044) in tumours with non-TNBC phenotype. AR and GRβ were more frequently expressed in ER+/PR+/HER2-tumours, while cytoplasmic MR was more often expressed in TNBC tumours (for all, p<0.0005). GRβ and AR were associated with decreased vimentin expression (p<0.005), indicating their association with attenuated EMT. Conclusion: Cytoplasmic MR expression is a strong predictor of local recurrence in non-metastatic breast cancer patients with non-TNBC tumour phenotype.

Type 1 collagen is an important part of the extracellular matrix and changes in its metabolism and distribution are essential in breast cancer induction and progression. Serum concentrations of type 1 collagen synthesis (aminoterminal propeptide (PINP)) and degradation markers (carboxyterminal telopeptide (ICTP)) have previously been studied in early and metastatic breast cancer, but no data are available on specific breast cancer subtypes. We assayed 662 preoperative serum samples for PINP and ICTP and 109 postoperative serum samples for ICTP. The results were linked to prospectively collected clinical data and the cases were divided into breast cancer subtypes for survival analyses. The concentrations of both pre- and postoperative ICTP serum levels increased linearly from ductal in situ carcinoma to stage I–II tumors, stage III tumors, and finally to those with concomitant primary metastases (preoperative ICTP, p = 0.009; postoperative ICTP, p = 0.016). High-preoperative ICTP levels were associated with better breast cancer-specific survival in connection with luminal-B-like (HER2-negative) tumors (p = 0.017), which was confirmed in Cox regression analysis (relative risk = 3.127; 95% confidence interval = 1.081–9.049, p = 0.035), when T-class (relative risk = 4.049; 95% confidence interval = 1.263–12.981; p = 0.019) and nodal status (relative risk = 3.896; 95% confidence interval = 1.088–13.959; p = 0.037) were included in the analysis. In patients with triple-negative breast cancer, a high-preoperative ICTP level was a significant predictor of local relapse-free survival in univariate (p = 0.0020) and multivariate analyses (relative risk = 13.04; 95% confidence interval = 1.354–125.5; p = 0.026; for T-class, relative risk = 2.128 and 95% confidence interval = 0.297–15.23; p = 0.452; for N-class, relative risk = 0.332 and 95% confidence interval = 0.033–3.307; p = 0.347). A preoperatively elevated serum ICTP level appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like (HER2-negative) subtypes.

Background: In Finland, breast cancers treated with neoadjuvant chemotherapy (NACT) are usually locally advanced and/or have an inflammatory phenotype. We evaluated early NACT responses in breast tumours and lymph nodes and their correlation with survival. Material and methods: We collected a retrospective dataset of 145 patients with very high-risk but non-metastasised breast cancers that were treated with NACT in a Finnish University Hospital between September 2013 and January 2019. The patients underwent magnetic resonance imaging (MRI) scans before beginning NACT and after every second NACT cycle thereafter. Results: The total pathological complete response rate was only 10.7% and breast cancer-specific survival (BCSS) at 24 months was 93.0%. The 2-year breast cancer-specific survival (BCSS) rate was 93.0%, but this varied from 86.5% for the triple-negative subtype to 100.0% for the luminal Alike subtype. Enlargement of the malignant axillary lymph nodes during the first two NACT cycles was associated with poor BCSS rates in HER2-negative patients (p ¼ .00003 in the univariate analysis; hazard ratio ¼ 26.3; 95% confidence interval ¼ 2.66-259.6; p ¼ .005 in the multivariate analysis). Furthermore, progression in the combined diameters of the breast tumours and axillary lymph nodes during the period between a patient's pre-treatment MRI and her MRI after two NACT cycles was also correlated with worse BCSS rates in both univariate and multivariate analyses. Conclusions: An early MRI assessment after two NACT cycles, specifically of the tumour's axillary lymph nodes, has the potential to predict short-term BCSS in patients with locally advanced HER2negative breast cancers.

ObjectivesBeing either young or old at the time of breast cancer diagnosis has been suggested as an indicator of a poor prognosis. We studied the effect of age at breast cancer onset in relation to survival, focusing in particular on biological subtypes and reproductive anamnesis.Design, setting and participantsPatients with early breast cancer (n=594) treated in a Finnish University Hospital during 2003–2013 were prospectively collected and followed in median 102 months.ResultsPatients with luminal A-like breast cancer were older than the patients with luminal B-like (HER2-positive) (p=0.045) or patients with the HER2-positive (non-luminal) subtype (p=0.029). Patients ≥70 years received substantially less adjuvant chemotherapy (p=1.5×10−9) and radiotherapy (p=5.9×10−7) than younger women. Nevertheless, the estimated 10-year breast cancer-specific rates of survival were 84.2%, 92.9% and 87.0% in age groups <41 years, 41–69 years and ≥70 years, respectively, with no statistical difference (p=0.115). Survival rates were also comparable between the three age groups when assessed separately in different biological subtypes, and for patients with metastatic breast cancer there was similarly no difference between the age groups. Later menarche (p=5.7×10−8) and high parity (p=0.000078) correlated with increased age at breast cancer diagnosis, but, according to the patients’ oestrogen receptor (ER) status, only among ER-positive patients.ConclusionsDespite the suggested undertreatment of older patients, we report excellent long-term outcomes in all age groups in this prospective cohort. Later endogenous endocrine exposure may cause delay in breast cancer onset, but the exact biology behind this phenomenon is so far unclear.

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