The incidence of discordant clinical and genomic risk in patients with invasive lobular or ductal carcinoma of the breast: a National Cancer Database Study

When molecular testing classifies breast tumors as low risk but clinical risk is high, the optimal management strategy is unknown. One group of patients who may be more likely to have such discordant risk are those with invasive lobular carcinoma of the breast. We sought to examine whether patients with invasive lobular carcinoma are more likely to have clinical high/genomic low-risk tumors compared to those with invasive ductal carcinoma, and to evaluate the impact on receipt of chemotherapy and overall survival. We conducted a cohort study using the National Cancer Database from 2010–2016. Patients with hormone receptor positive, HER2 negative, stage I-III breast cancer who underwent 70-gene signature testing were included. We evaluated the proportion of patients with discordant clinical and genomic risk by histology using Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models with and without propensity score matching. A total of 7399 patients (1497 with invasive lobular carcinoma [20.2%]) were identified. Patients with invasive lobular carcinoma were significantly more likely to fall into a discordant risk category compared to those with invasive ductal carcinoma (46.8% versus 37.1%, p < 0.001), especially in the clinical high/genomic low risk subgroup (35.6% versus 19.2%, p < 0.001). In unadjusted analysis of the clinical high/genomic low-risk cohort who received chemotherapy, invasive ductal carcinoma patients had significantly improved overall survival compared to those with invasive lobular carcinoma (p = 0.02). These findings suggest that current tools for stratifying clinical and genomic risk could be improved for those with invasive lobular carcinoma to better tailor treatment selection.

Invasive Lobular Carcinoma Has Worse Outcome Compared with Invasive Ductal Carcinoma in Stage IV Breast Cancer with Bone-Only Metastasis

Background: Invasive lobular carcinoma (ILC) is more likely to be bone metastasis than invasive ductal carcinoma (IDC). However, the prognosis for bone metastasis in ILC and IDC is barely known. So, the aim of this study was to investigate the difference of prognosis between ILC and IDC accompany by bone metastasis. Methods: We evaluated the women with bone-only metastasis of defined IDC or ILC, reported to the Surveillance, Epidemiology and End Results program from 2010 to 2016. Pearson's chi-squared test was used to compare the difference of clinicopathologic factors between IDC and ILC. Univariate and multivariate analyses were performed to verify the effects of histological types (IDC and ILC) and other clinicopathologic factors on the overall survival (OS) and cancer-special survival (CSS). Results: Overall, 3647 patients with IDC and 945 patients with ILC met the inclusion criteria and were analyzed in our study. The patients with ILC were more likely to be older, lower histological grade and higher proportion of HR+/HER2- subtype. But less treatment was applied to ILC than IDC, such as surgery of the breast, radiation and chemotherapy. Compared patients with IDC, the patients with ILC showed worse OS (median OS 36 and 42 months respectively, p<0.001) and CSS (median CSS 39 and 45 months respectively, p<0.001), especially in subgroups with HR+/HER2- subtype [OS (Hazard ration: 1.501, 95% CI [1.270-1.773], p<0.001); CSS (Hazard ration: 1.529, 95% CI [1.281-1.825], p<0.001)], lower histological grade (Ⅰ-Ⅱ) [OS (Hazard ration: 1.411, 95% CI [1.184-1.683], p<0.001); CSS (Hazard ration: 1.488, 95% CI [1.235-1.791], p<0.001)] or tumor burden, such as T0-2 [OS (Hazard ration: 1.693, 95% CI [1.368-2.096], p<0.001); CSS (Hazard ration: 1.76, 95% CI [1.405-2.205], p<0.001)] and N1-2 [OS (Hazard ration: 1.451, 95% CI [1.171-1.799], p=0.001); CSS (Hazard ration: 1.488, 95% CI [1.187-1.865], p=0.001)]. Furthermore, older age, black race, unmarried status, higher tumor burden (T3-4 and N3), triple-negative subtype and higher histological grade were independent risk factors for both OS and CSS. Surgery of the breast and chemotherapy could significantly improve the prognosis for patients. Conclusion: The patients with ILC have worse outcomes compared with that of IDC when bone-only metastasis occurred to them, especially in subgroups with lower histological grade or tumor burden. More effective treatment measures may be needed for ILC, such as cyclin-dependent kinase 4/6 inhibitors (CDKs), new targeted drugs, etc.

Metastatic Signet-Ring-Cell Carcinoma of Bladder From Breast Invasive Lobular Carcinoma Found By CT: A Case Report And Literature Review

Background: Secondary bladder tumors are relatively rare in all bladder tumors, while bladder metastases from breast cancer were rarely reported. And interestingly, signet-ring differentiation may appear in metastases from a breast invasive lobular carcinoma regardless of whether or not the primary breast tumor had signet-ring cells, which may cause diagnostic uncertainty.Case presentation: We report a case of a 55-year-old female patient with diffuse bladder thickening as the chief complaint. There was no special clinical manifestation, while cystoscopy showed multiple scattered red protuberances and the biopsy suggested signet-ring-cell carcinoma. Result of gastroscopy suggested poorly differentiated adenocarcinoma with signed-ring cells. Considering the patient's previous history of invasive lobular carcinoma of the breast, chronic myeloid leukemia and metastatic endometrial carcinoma from the breast, we performed the immunohistochemistry and the results indicated that signet-ring-cell carcinomas of the stomach and bladder originated from the breast invasive lobular carcinoma. we performed Positron Emission Tomography/Computed Tomography (PET/CT) and the results showed that there were multiple bone metastases already.Conclusion: This is the first English case report of invasive lobular carcinoma of breast metastasizing to uterus, stomach, bladder and bones with multiple signet-ring-cell variations. We also focus on the Computed Tomography (CT), immunohistochemistry (IHC) and cystoscopy findings and share the clinical diagnosis ideas summarized by this case.