Pain, sensory disturbances and psychological distress are common sequelae after treatment of ductal carcinoma <i>in situ</i>: a cross-sectional study

<p>Sequelae such as pain, sensory disturbances and psychological distress are well known after treatment for invasive breast cancer (IBC). Patients treated for ductal carcinoma <i>in situ</i> (DCIS) receive a similar treatment as low-risk IBC. The aim of this cross-sectional study was to describe prevalence of postoperative pain, sensory disturbances, psychological distress and rehabilitation needs among Danish women with DCIS.</p> <p><b>Methods:</b> A total of 574 women treated for DCIS in Denmark in 2013 and 2014 were enrolled and 473 (82%) completed a detailed questionnaire on demographic factors, pain, sensory disturbances, psychological aspects and rehabilitation needs 1–3 years after surgery.</p> <p><b>Results:</b> Median age was 60 years. A total of 33% of patients reported any pain and 12% reported moderate to severe pain in the area of surgery. Younger age (<50 years OR 4.7 (95% CI: 1.6–14.0, <i>p</i> = 0.006)), aged 50 to 65 years OR 2.8 (95% CI: 1.1–7.0, <i>p</i> = 0.02) and anxiety and depression (measured by HADS_total >15 OR of 3.1 (95% CI: 1.5–6.3, <i>p</i> = 0.003)) were significantly associated with moderate to severe pain. Approximately one-third of the patients reported sensory disturbances such as pins and needles (32%), numbness (37%) and painful itch (30%) and 94 women (20%) reported anxiety ≥8, 26 (6%) depression and 51 (11%) reported distress.</p> <p><b>Conclusions:</b> This cross-sectional study showed that women treated for DCIS suffered from pain, sensory disturbances and psychological impairment and had unmet rehabilitation needs. Further research is warranted, specifically addressing rehabilitation after diagnosis and treatment of DCIS.</p

Axillary lymph node dissection in breast cancer patients after sentinel node biopsy^*

Axillary lymph node dissection in breast cancer patients after sentinel node biopsy<a href="#FN0001" target="_blank">^*</a

Breast conserving surgery versus mastectomy: overall and relative survival—a population based study by the Danish Breast Cancer Cooperative Group (DBCG)

<p><b>Background:</b> Observational studies have pointed at a better survival after breast conserving surgery (BCS) compared with mastectomy. The aim of the present study was to evaluate whether this remains true when more extensive tumor characteristics and treatment data were included.</p> <p><b>Methods:</b> The cohort included patients registered after primary surgery for early invasive breast cancer in the database of the Danish Breast Cancer Cooperative Group, in the period 1995–2012. The cohort was divided into three groups: (i) patients who primarily had a mastectomy, (ii) patients treated by BCS, and (iii) patients who primarily had BCS and then mastectomy [intention to treat (ITT) by BCS]. The association between overall mortality and standard mortality ratio (SMR) and risk factors was analyzed in univariate and multivariate Poisson regression models.</p> <p><b>Results:</b> A total of 58,331 patients were included: 27,143 in the mastectomy group, 26,958 in the BCS group, and 4230 in the BCS-ITT group. After adjusting for patient and treatment characteristics, the relative risk (RR) was 1.20 (95% CI: 1.15–1.25) after mastectomy and 1.08 (95% CI: 1.01–1.15) after BCS first and then mastectomy, as compared to BCS. Statistically significant interactions were not observed for age, period of treatment, and nodal status, but patients with Charlson’s Comorbidity Index (CCI) score 2+ had no increased mortality after mastectomy, as opposed to patients with CCI 0–1. Loco-regional radiation therapy (RT) in node positive patients did not reduce the increased risk associated with mastectomy [RR = 1.28 (95% CI 1.19–1.38)].</p> <p><b>Conclusion:</b> Patients assigned to BCS have a better survival than patients assigned to mastectomy. Residual confounding after adjustment for registered characteristics presumably explained the different outcomes, thus consistent with selection bias. Diversities in RT did not appear to explain the observed difference in survival after BCS and mastectomy.</p

Clinical characteristics of DCTB tissue specimens.

<p>Clinical characteristics of DCTB tissue specimens.</p

2D PAGE and 2D Western blot analysis of BLCAP protein spot patterns.

<p>(A) COS-1 cells transfected with pZeoSV2 empty vector and labeled with ³⁵S-methionine. (B) COS-1 cells transfected with pZeoSV2– BLCAP overexpressing construct and labeled with ³⁵S-methionine. Radioactive metabolic labeling (³⁵S-methionine) of COS-1 cells was used to ensure the highest detection sensitivity. (C) 2D Western blot of COS-1 cells transfected with pZeoSV2– BLCAP construct detected with anti-BLCAP antibody (10 sec film exposure). (D) 2D gel of proteins from breast tumor 63 stained with silver. (E) 2D Western blot of protein lysate from breast tumor 63 (see D) reacted with anti-BLCAP antibody (1 min film exposure). The positions of the BLCAP protein in the 2D-PAGE gels and corresponding 2D Western blots, are indicated by black arrows. The positions of several reference proteins are indicated by red arrows: ACTB – beta actin; ENO1 -alpha enolase 1; CANX – calnexin; PDI - Protein disulfide-isomerase; TUBA1A - tubulin alpha-1A chain; YWHAZ - 14-3-3 protein zeta/delta. The identity of all reference spots were confirmed by MS analysis.</p

Clinicopathological correlation of BLCAP expression in 2,197 sample TMA.

*<p>Kruskal-Wallis one way analysis of variance on ranks.</p>**<p>Mann-Whitney rank-sum test.</p

Differential expression of BLCAP in tumor samples.

<p>The DCTB 123 patient set, including normal, tumor and lymph node metastasis samples (A), or a subset of matched 62 normal and tumor samples (B) were analyzed by quantitative IHC. Mean intensity scores for each group are indicated by red lines.</p

Expression analysis of BLCAP by quantitative IHC of normal specimens (blue bars) and corresponding tumor samples (red bars) of 62 matched cases from the DCTB dataset.

<p>Illustrative IHC images are shown for normal and tumor samples with weak immunoreactivity (N11 and T76, respectively), and for normal and tumor samples showing substantial immunoreactivity for BLCAP (N14 and T63, respectively). Magnification 20X.</p

Immunohistochemical expression analysis of BLCAP in FFPE breast tissue samples.

<p>(A) No immunostaining was observed in a normal breast tissue section reacted with BLCAP antibody preincubated with immunizing peptide. (B) Immunohistochemical staining of BLCAP protein in a normal breast tissue sample demonstrated the presence of the BLCAP antigen in luminal epithelial cells with weak cytoplasmic expression (black arrow). Marked nuclear expression was also observed occasionally (red arrow). Yellow arrow points to a vessel with moderate immunoreactivity for BLCAP. (C) In a few cases IHC analysis of tumor samples showed that BLCAP was expressed in tumor cells with weak cytoplasmic expression (red arrow). (D) Most cases showed moderate to strong cytoplasmic expression with no detectable nuclear presence (red arrow) but in some cases (E) we could observe strong nuclear expression of BLCAP (red arrow). (F) In a few cases, samples were heterogenous with some cells showing distinct perinuclear immunoreactivity for BLCAP (red arrow). (G) Malignant cells showed stronger immunoreactivity (red arrows) than adjacent normal-looking ducts (black arrow), demonstrating up-regulation of this protein in tumor cells. Yellow arrows point to vessels with strong immunoreactivity for BLCAP. (H) We also observed up-regulation of BLCAP in early lesions where lobular carcinoma in situ cells showed overexpression of this protein (grey arrows) in relation to normal adjacent areas (black arrow), and at levels comparable to invasive carcinoma cells (red arrow).</p

FABP7 and HMGCS2 Are Novel Protein Markers for Apocrine Differentiation Categorizing Apocrine Carcinoma of the Breast

<div><p>Apocrine carcinoma of the breast is a distinctive malignancy with unique morphological and molecular features, generally characterized by being negative for estrogen and progesterone receptors, and thus not electable for endocrine therapy. Despite the fact that they are morphologically distinct from other breast lesions, no standard molecular criteria are currently available for their diagnosis. Using gel-based proteomics in combination with mass spectrometry and immunohistochemistry we have identified two novel markers, HMGCS2 and FABP7 that categorize the entire breast apocrine differentiation spectrum from benign metaplasia and cysts to invasive stages. Expression of HMGCS2 and FABP7 is strongly associated with apocrine differentiation; their expression is retained by most invasive apocrine carcinomas (IAC) showing positive immunoreactivity in 100% and 78% of apocrine carcinomas, respectively, as compared to non-apocrine tumors (16.7% and 6.8%). The nuclear localization of FABP7 in tumor cells was shown to be associated with more aggressive stages of apocrine carcinomas. In addition, when added to the panel of apocrine biomarkers previously reported by our group: 15-PGDH, HMGCR and ACSM1, together they provide a signature that may represent a golden molecular standard for defining the apocrine phenotype in the breast. Moreover, we show that combining HMGCS2 to the steroidal profile (HMGCS2+/Androgen Receptor (AR)+/Estrogen Receptor(ER)-/Progesteron Receptor (PR)- identifies IACs with a greater sensitivity (79%) as compared with the steroidal profile (AR+/ER-/PR-) alone (54%). We have also presented a detailed immunohistochemical analysis of breast apocrine lesions with a panel of antibodies against proteins which correspond to 10 genes selected from published transcriptomic signatures that currently characterize molecular apocrine subtype and shown that except for melanophilin that is overexpressed in benign apocrine lesions, these proteins were not specific for morphological apocrine differentiation in breast.</p></div