Histological grade provides significant prognostic information in addition to breast cancer subtypes defined according to St Gallen 2013.

BACKGROUND: The St Gallen surrogate definition of the intrinsic subtypes of breast cancer consist of five subgroups based on estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2), and Ki-67. PgR and Ki-67 are used for discriminating between the 'Luminal A-like' and 'Luminal B-like (HER2-negative)' subtypes. Histological grade (G) has prognostic value in breast cancer; however, its relationship to the St Gallen subtypes is not clear. Based on a previous pilot study, we hypothesized that G could be a primary discriminator for ER-positive/HER2-negative breast cancers that were G1 or G3, whereas Ki-67 and PgR could provide additional prognostic information specifically for patients with G2 tumors. To test this hypothesis, a larger patient cohort was examined. PATIENTS AND METHODS: Six hundred seventy-one patients (≥35 years of age, pT1-2, pN0-1) with ER-positive/HER2-negative breast cancer and complete data for PgR, Ki-67, G, lymph node status, tumor size, age, and distant disease-free survival (DDFS; median follow-up 9.2 years) were included. RESULTS: 'Luminal A-like' tumors were mostly G1 or G2 (90%) whereas 'Luminal B-like' tumors were mostly G2 or G3 (87%) and corresponded with good and poor DDFS, respectively. In 'Luminal B-like' tumors that were G1 (n = 23), no metastasis occurred, whereas 14 of 40 'Luminal A-like' tumors that were G3 metastasized. In the G2 subgroup, low PgR and high Ki-67 were associated with an increased risk of distant metastases, hazard ratio (HR) and 95% confidence interval (CI) 1.8 (0.95-3.4) and 1.5 (0.80-2.8), respectively. CONCLUSIONS: Patients with ER-positive/HER2-negative/G1 breast cancer have a good prognosis, similar to that of 'Luminal A-like', while those with ER-positive/HER2-negative/G3 breast cancer have a worse prognosis, similar to that of 'Luminal B-like', when assessed independently of PgR and Ki-67. Therapy decisions based on Ki-67 and PgR might thus be restricted to the subgroup G2.

Comparison of margin assessment by radial and shave sections in wide local excision specimens for invasive carcinoma of the breast.

AIMS: Standard margin assessment of breast carcinoma surgical specimens uses radial sections perpendicular to the margin. Shave sections assess a larger surface area of margin than radial sections. The aim was to assess the value of additional shave sections of the margin. METHODS AND RESULTS: Both types of section were used to assess 471 wide local excision specimens for invasive carcinoma. One hundred and seventy-nine specimens had positive margins: only radial margins were involved (tumour within 5 mm of margin) in 76, only shave margins in 45, and both shave and radial margins in 58. Residual carcinoma was found in re-excision specimens (immediate or later) in 43% when the closest distance to the radial margin was 0-1 mm, 25% for 2-4 mm, 18% for 5-9 mm and 13% for >9 mm. Residual carcinoma was found in 44% of specimens if any shave section was positive and in 9% if all shaves were negative. Residual carcinoma was found in 32% if either radial or shave sections were positive and in 4% if neither was positive. CONCLUSIONS: The combination of radial and shave sections appears to be good at separating patients into two groups with high and low risk of residual carcinoma.

Prognostic significance of Nottingham histologic grade in invasive breast carcinoma.

PURPOSE: The three strongest prognostic determinants in operable breast cancer used in routine clinical practice are lymph node (LN) stage, primary tumor size, and histologic grade. However, grade is not included in the recent revision of the TNM staging system of breast cancer as its value is questioned in certain settings. MATERIALS AND METHODS: This study is based on a large and well-characterized consecutive series of operable breast cancer (2,219 cases), treated according to standard protocols in a single institution, with a long-term follow-up (median, 111 months) to assess the prognostic value of routine assessment of histologic grade using Nottingham histologic grading system. RESULTS: Histologic grade is strongly associated with both breast cancer-specific survival (BCSS) and disease-free survival (DFS) in the whole series as well as in different subgroups based on tumor size (pT1a, pT1b, pT1c, and pT2) and LN stages (pN0 and pN1 and pN2). Differences in survival were also noted between different individual grades (1, 2, and 3). Multivariate analyses showed that histologic grade is an independent predictor of both BCSS and DFS in operable breast cancer as a whole as well as in all studied subgroups. CONCLUSION: Histologic grade, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive breast cancer and should be incorporated in breast cancer staging systems.

The reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast.

AIM: To assess the reliability of assessment of oestrogen receptor expression on needle core biopsy specimens of invasive carcinomas of the breast. Previous studies have mostly been small, with a range of agreement from 62% to 100%. METHODS: Retrospective audit of 338 tumours surgically excised within 60 days of core biopsy, that had had oestrogen receptor assessed on both the core biopsy and tumour specimens. Surgical specimens were incised when fresh to ensure good fixation. External controls including a weakly positive tumour were included in each immunohistochemistry run. RESULTS: Oestrogen receptor expression was bimodal, with H score in both specimens of either 0 or >50 in 96% of tumours. Using H score cut-off of 10 for positivity, there was an agreement between core and excision in 334 of 338 tumours (98.8%). All discrepancies were between weakly positive and negative tumours. Intratumoral heterogeneity could explain the one tumour that was negative on core and positive on excision. H score tended to be slightly higher on core than excision (means 146 and 136). Better fixation on the core is the most likely explanation for this and for the three tumours that were positive on core and negative on excision. Repeat staining on tumours with discrepant results gave similar results in all except one case. An internal control was present in 97% of excisions and 55% of cores of oestrogen receptor-negative tumours; the internal control stained positively in all except two sections. CONCLUSION: Oestrogen receptor can be assessed reliably on needle core biopsies of invasive carcinomas of the breast.

Correlation of histologic prognostic factors in core biopsies and therapeutic excisions of invasive breast carcinoma.

Breast core biopsy is one of the major nonoperative methods of diagnosis. Increasingly, there is also a need to provide prognostic data to facilitate timely patient management. We present the results from 500 patients with invasive breast carcinoma, who underwent core biopsy followed by a therapeutic surgical procedure. Grade and type of the invasive and in situ carcinoma, together with the presence or absence of vascular invasion, were determined in both biopsy and definitive surgical excision and the results compared. There was 67% agreement with overall grade (kappa value 0.48), with scores for tubule formation, pleomorphism, and mitotic scoring achieving values of 82%, 73%, and 58%, respectively. Only 60% of grade 1 and 2 carcinomas showed concordance, but 84% of grade 3 tumors showed agreement between core and excision results. Tumor typing, vascular invasion, and grading of ductal carcinoma in situ had agreement values of 74%, 69%, and 65%, respectively. The major problem with assessing prognostic factors on needle biopsy specimens is undersampling of the most informative areas. However, in those patients in whom preoperative assessment of prognostic factors is most likely to be beneficial, i.e., those with grade 3 carcinomas, a high level of agreement was achieved in this large study.