Ulrik Narbe

Background Invasive lobular carcinoma (ILC) is a risk factor for positive margins after breast-conserving surgery (BCS). This retrospective observational study examined whether the presence of residual cancer cells in re-excision is associated with ILC or locoregional recurrence. Methods Patients (aged > 18 years) who underwent BCS for invasive or in situ cancer at two sites (2015–2017) were included. Data were retrieved from medical records and the Swedish National Breast Cancer Register. The primary endpoint was residual cancer cells in first re-excision, and secondary endpoints were locoregional recurrence-free interval (LRFi), distant recurrence-free interval, and breast cancer-specific survival. Results In total, 770 patients were included, of whom 132 (17.1%) had positive margins; 130/132 underwent re-excision, and residual cancer cells were detected in 80 (61.5%). Residual cancer cells were weakly and not significantly associated with histological subtype (ILC versus invasive carcinoma of no special type (NST)), but associated with number of positive margins, mammographic lesion size, and pathological extent (all P < 0.05). After a median follow-up time of 7.0 years, locoregional recurrence was diagnosed in 34/721 patients (4.7%). There was no evidence of a difference in LRFi by margin status, residual cancer cells, or histological subtype (all P > 0.4). Molecular subtypes and adjuvant therapies were associated with the risk of locoregional recurrence. Conclusion The presence of residual cancer cells in the first re-excision is not associated with locoregional recurrence risk and only weakly associated with ILC. Number of margins involved and lesion size are predictive of residual cancer cells and might support surgical decision-making at re-excision.

Previous studies have shown that high intratumoral stromal content is associated with a worse prognosis in breast cancer, especially in the triple-negative subtype. However, contradictory results have been reported for estrogen-receptor-positive (ER+) breast cancer, indicating that the prognostic role of intratumoral stromal content may be subtype-dependent. In this study, we investigated the importance of intratumoral stromal content for breast cancer-specific mortality (BCM) in a well-defined subgroup (n = 182) of ER+/human-epidermal growth-factor-receptor-2 negative (HER2−) invasive lobular breast cancer (ILC). The intratumoral stromal content was assessed on hematoxylin–eosin-stained whole sections and graded into high stroma (>50%) or low stroma (≤50%). A total of 82 (45%) patients had high-stroma tumors, and 100 (55%) had low-stroma tumors. High-stroma tumors were associated with a lower Nottingham histological grade, low Ki67, and a luminal A-like subtype. After a 10-year follow-up, the patients with high-stroma tumors had a lower BCM (HR: 0.43, 95% CI: 0.21–0.89, p = 0.023) in univariable analysis. Essentially the same effect was found in both the multivariable analysis (10-year follow-up) and univariable analysis (25-year follow-up), but these findings were not strictly significant. In ER+/HER2− ILC, high intratumoral stromal content is an easily assessable histological indicator of a good prognosis.

Background: The St Gallen 2019 guidelines for primary therapy of early breast cancer recommend omission of completion axillary lymph node dissection (cALND), regardless of histological type, in patients with one or two sentinel lymph node (SLN) metastases. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with four or more axillary lymph node (ALN) metastases. The aim of this study was to estimate the proportion of patients with invasive lobular cancer (ILC) versus invasive ductal cancer of no special type (NST) with one or two SLN metastases for whom cALND would have led to a recommendation for adjuvant chemotherapy. Methods: Patients with ILC and NST who had surgery between 2014 and 2017 were identified in the National Breast Cancer Register of Sweden. After exclusion of patients with incongruent or missing data, those who fulfilled the St Gallen 2019 criteria for cALND omission were included in the population-based study cohort. Results: Some 1886 patients in total were included in the study, 329 with ILC and 1507 with NST. Patients with ILC had a higher metastatic nodal burden and were more likely to have a luminal A-like subtype than those with NST. The prevalence of at least four ALN metastases was higher in ILC (31.0 per cent) than NST (14.9 per cent), corresponding to an adjusted odds ratio of 2.26 (95 per cent c.i. 1.59 to 3.21). Luminal A-like breast cancers with four or more ALN metastases were over-represented in ILC compared with NST, 52 of 281 (18.5 per cent) versus 43 of 1299 (3.3 per cent) (P < 0.001). Conclusion: Patients with ILC more often have luminal A-like breast cancer with at least four nodal metastases. Omission of cALND in patients with luminal A-like invasive lobular cancer and one or two SLN metastases warrants future attention as there is a risk of nodal understaging and undertreatment in one-fifth of patients.

Background: Invasive lobular carcinoma (ILC) has distinguishing features when compared to invasive ductal carcinoma of no special type (NST). In this study, we explored the distributional and prognostic characteristics of circulating tumor cells (CTCs) in metastatic ILC and NST. Materials and methods: Patients were included in an observational trial (ClinicalTrials.gov NCT01322893) with ILC (n = 28) and NST (n = 111). CTC count (number/7.5 mL blood) was evaluated with serial sampling (CellSearch). The primary endpoint was progression-free survival (PFS). Results: The CTC counts were higher in ILC (median 70) than in NST cases (median 2) at baseline (p < 0.001). The evidence for ≥5 CTCs as a prognostic factor for PFS in ILC was weak, but stronger with higher cut-offs (CTC ≥ 20: hazard ratio (HR) 3.0, p = 0.01) (CTC ≥ 80: HR 3.6, p = 0.004). In NST, however, the prognostic effect of CTCs ≥5 was strong. Decline in CTC count from baseline to three months was associated with improved prognosis in ILC and NST. Conclusions: The number of CTCs is higher in ILC than in NST, implying that a higher CTC cut-off could be considered for ILC when applying the CellSearch technique.

Purpose According to the 2017 St Gallen surrogate definitions of the intrinsic subtypes, Ki67, progesterone receptor (PR) and Nottingham histological grade (NHG) are used for prognostic classification of estrogen receptor (ER) positive/HER2-negative breast cancer into luminal A- or luminal B-like. The aim of the present study was to investigate if additional biomarkers, related to endocrine signaling pathways, e.g., amplified in breast cancer 1 (AIB1), androgen receptor (AR), and G protein-coupled estrogen receptor (GPER), can provide complementary prognostic information in a subset of ER-positive/HER-negative invasive lobular carcinoma (ILC). Methods Biomarkers from 224 patients were analyzed immunohistochemically on tissue microarray. The primary endpoint was breast cancer mortality (BCM), analyzed with 10- and 25-year follow-up (FU). In addition, the prognostic value of gene expression data for these biomarkers was analyzed in three publicly available ILC datasets. Results AIB1 (high vs. low) was associated to BCM in multivariable analysis (adjusted for age, tumor size, nodal status, NHG, Ki67, luminal-like classification, and adjuvant systemic therapy) with 10-year FU (HR 6.8, 95% CI 2.3–20, P = 0.001) and 25-year FU (HR 3.0, 95% CI 1.1–7.8, P = 0.03). The evidence of a prognostic effect of AIB1 could be confirmed by linking gene expression data to outcome in independent publicly available ILC datasets. AR and GPER were neither associated to BCM with 10-year nor with 25-year FU (P > 0.33). Furthermore, Ki67 and NHG were prognostic for BCM at both 10-year and 25-year FU, whereas PR was not. Conclusions AIB1 is a new putative prognostic biomarker in ER-positive/HER2-negative ILC.

The aim of the present study was to investigate the long-term impact of prognostic factors in invasive lobular carcinoma (ILC) of the breast, with a primary focus on Ki67 and histological grade, alone and in combination with estrogen receptor (ER). One hundred and ninety two well-characterised patients with ILC were included in the study. Ki67, histological grade and ER were evaluated and combined into a prognostic index (KiGE). All grade 1 tumours and ER-positive (ER+) grade 2 tumours with Ki67 ≤ 30% were classified as low-KiGE and all the others as high-KiGE. Overall, 31% of the patients have died from breast cancer. The median follow-up of the patients still alive was 21 years. Age, tumour size, axillary lymph node status (nodal status), histological grade, Ki67 and KiGE were significant prognostic factors for breast cancer mortality (BCM) in univariable analysis. In a multivariable model, adjusted for adjuvant treatment, age and progesterone receptor (PgR), the strongest prognostic factors for BCM were: Nodal status (hazard ratio (HR) = 2.9, 95% confidence interval (95% CI): 1.4-6.1), KiGE (HR = 2.0, 95% CI: 1.1-3.6), and tumour size (HR = 1.9, 95% CI: 0.98-3.8). By combining these three factors, 37% of the ILC’s could be further divided into a low-risk group, consisting of node negative small (≤ 20 mm) low-KiGE tumours, with a BCM of 5% (95% CI: 1-13%) at 10 years and 12% (95% CI: 5-22%) at 20 years follow-up. None of these patients recieved chemotherapy and only 2 recieved endocrine treatment with tamoxifen. The combination of Ki67, histological grade and ER into KiGE, together with tumour size and nodal status make it possible to identify a large group of ILC patients with such a good long-term prognosis that chemotherapy can be safely avoided and exclusion of endocrine therapy considered.