Invasive Lobular vs. Ductal Breast Cancer: A Stage-Matched Comparison of Outcomes

Background  

Invasive lobular breast cancer (ILC) is less common than invasive ductal breast cancer (IDC), more difficult to detect mammographically, and usually diagnosed at a later stage. Does delayed diagnosis of ILC affect survival? We used a national registry to compare outcomes of patients with stage-matched ILC and IDC.     

Invasive Lobular Carcinoma of the Breast

Invasive lobular carcinoma of the breast is a distinct histologic type with specific clinical, radiologic, and microscopic features, which is increasing in incidence in the Western World. Routine pathologic prognostic factors, including grade, lymph node stage, and size are of significance in predicting outcome in this group of patients who, overall, have survival comparable to those with other subtypes of breast cancer. Variants, however, are seen and these, as well as other standard factors such as histologic grade, have prognostic significance and should be recorded in pathology reports.     

Editorial: Applying Margin Consensus Guidelines to Invasive Lobular Carcinoma of the Breast

Annals of Surgical Oncology -     

Re-Excision Rates of Invasive Ductal Carcinoma with Lobular Features Compared with Invasive Ductal Carcinomas and Invasive Lobular Carcinomas of the Breast

Background

Invasive ductal carcinoma (IDC) with lobular features (IDC-L) is not recognized as a subtype of breast cancer. We previously showed that IDC-L may be a variant of IDC with clinicopathological characteristics more similar to invasive lobular carcinoma (ILC). We sought to determine the re-excision rates of IDC-L compared with ILC and IDC, and the feasibility of diagnosing IDC-L on core biopsies.

Methods

Surgical procedure, multiple tumor foci, tumor size, and residual invasive carcinoma on re-excision were recorded for IDC-L (n = 178), IDC (n = 636), and ILC (n = 251). Re-excision rates were calculated by excluding mastectomy as first procedure cases and including only re-excisions for invasive carcinoma. Slides of correlating core biopsies for IDC-L cases initially diagnosed as IDC were re-reviewed.

Results

For T2 tumors (2.1–5.0 cm), re-excision rates for IDC-L (76 %) and ILC (88 %) were higher than that for IDC (42 %) (p = 0.003). Multiple tumor foci were more common in IDC-L (31 %) and ILC (26 %) than IDC (7 %) (p < 0.0001), which was a significant factor in higher re-excision rates when compared with a single tumor focus (p < 0.001). Ninety-two of 149 patients (62 %) with IDC-L were diagnosed on core biopsies. Of the 44 patients initially diagnosed as IDC, 30 were re-reviewed, of which 24 (80 %) were re-classified as IDC-L.

Conclusions

Similar to ILC, re-excision rates for IDC-L are higher than IDC for larger tumors. Patients may need to be counseled about the higher likelihood of additional procedures to achieve negative margins. This underscores the importance of distinguishing IDC-L from IDC on core biopsies.     

An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular Breast Cancer

The Oncotype DX breast cancer assay (Genomic Health, Redwood City, CA) is increasingly being used to guide treatment decisions for patients with early stage, hormone‐positive, Her‐2‐negative breast cancer. The utility of the Oncotype DX in decision making for treatment of invasive lobular carcinoma (ILC) has not been investigated as the results reported by Genomic Health are largely in a population with invasive ductal carcinoma (IDC). The authors hypothesized that the Oncotype DX recurrence score (RS) distribution for ILC is different than that for IDC. We performed a retrospective analysis of early stage breast cancer patients treated at Penn State Cancer Institute from 2001 to 2011 and identified 102 patients with ILC. We also pulled RS data from our institution's prospective registry of consecutive patients with early stage IDC treated during the same time period. Median follow‐up was 55 months. We found that the RS distribution for ILC differed significantly from that of IDC (p = 0.024). We also found a statistically significant difference in the RS distribution between the pure ILC and pleomorphic ILC subtypes (p = 0.027). The Oncotype DX RS distribution in ILC is unique, differing significantly from that in ductal carcinoma. Consequently, the clinical usefulness and cost‐effectiveness of the Oncotype DX in guiding treatment for ILC should be further investigated.     

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

BackgroundInvasive lobular carcinoma (ILC) is more likely to have 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 accompanied by bone metastasis.MethodsWe 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 χ² test was used to compare the differences 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-specific survival (CSS).ResultsOverall, 3,647 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 and to have lower histological grade and a higher proportion of the HR*/HER2− subtype. However, less treatment was administered to ILC than IDC, such as surgery of the breast, radiation, and chemotherapy. Compared to patients with IDC, 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 ratio: 1.501, 95% CI 1.270–1.773, p < 0.001; CSS, hazard ratio: 1.529, 95% CI 1.281–1.825, p < 0.001), lower histological grade (I–II) (OS, hazard ratio: 1.411, 95% CI 1.184–1.683, p < 0.001; CSS, hazard ratio: 1.488, 95% CI 1.235–1.791, p < 0.001), or tumor burden, such as T_0–2 (OS, hazard ratio: 1.693, 95% CI 1.368–2.096, p < 0.001; CSS, hazard ratio: 1.76, 95% CI 1.405–2.205, p < 0.001) and N_1–2 (OS, hazard ratio: 1.451, 95% CI 1.171–1.799, p = 0.001; CSS, hazard ratio: 1.488, 95% CI 1.187–1.865, p = 0.001). Furthermore, older age, black race, unmarried status, higher tumor burden (T_3–4 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.ConclusionPatients with ILC have worse outcomes compared to those with IDC when associated with bone-only metastasis, 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, new targeted drugs, etc.     

Landmark Clinical Trials Influencing Surgical Management of Non‐invasive and Invasive Breast Cancer

The surgical management of breast cancer has changed considerably since the use of the Halstedian radical mastectomy early in the 20th century. Over the last 50 years, several landmark clinical trials from the USA and Europe have resulted in a paradigm shift in the management of breast cancer toward less radical forms of surgery with the combined use of multi‐modality treatments including systemic chemotherapy, endocrine therapy, and radiotherapy. Advances in such research have established a new worldwide standard of care for breast cancer surgical management and treatment, which has become more patient centric and which places a higher emphasis on cosmesis and improved patient quality of life. In this chapter, we review the landmark clinical trials that have influenced surgical management for non‐invasive and invasive breast cancer and that serve to guide current clinical practices to date.     

Invasive Breast Cancer: Recognition of Molecular Subtypes

SUMMARY: Molecular profiling has fundamentally changed our understanding of breast cancer in the last 10 years, by creating a new taxonomy of breast cancers based on the expression patterns of so-called 'intrinsic genes'. Hierarchical clustering analyses performed on microarray-based gene expression profiles of breast cancers defined distinct breast cancer subgroups (luminal type A/B, HER2-enriched type, basal-like type). Since the initial landmark study by Perou et al., the concept of intrinsic breast cancer subtypes has been corroborated and expanded by several independent research groups. Further studies revealed individual properties of the intrinsic subgroups regarding the clinical course and the responsiveness to chemotherapy. The new gene expression profile-based taxonomy of breast cancer has been enthusiastically embraced by the scientific community and hailed as a major breakthrough on the way to individually tailored therapies. However, validation of the gene signatures in prospective studies is necessary before accepting these new technologies in daily clinical practice. In this review, the current data regarding the intrinsic subtypes and the associated clinical implications as well as the methodology of molecular profiling and possible use of immunohistochemistry in identifying intrinsic subtypes are discussed.     

Invasive Lobular Carcinoma of the Male Breast: A Rare Histology in an Uncommon Disease

Summary

Background

Breast cancer in men is an uncommon disease. Nearly all cases of male breast cancer originate in the terminal ductulolobular unit, with exceedingly rare reports of lobular carcinoma in men. Invasive lobular cancer is found in no more than 1-2% of male breast cancer cases. Most of what is known about this disease is in the form of approximately 30 case reports in the literature.

Case Report

We report the case of a 52-year-old man who presented at our institution with a lump in his left breast. Ultrasound-guided biopsy revealed an invasive lobular cancer. The rare histological type was confirmed by the result of the histological examination of the mastectomy specimen. The treatment was completed by dose dense chemotherapy, radiation, and endocrine therapy.

Conclusion

Even though lobular structures are quite infrequent in the normal male, sporadic cases of invasive lobular breast cancer have been described. A short overview will be given in this case report.Key Words: Male breast cancer, Lobular carcinoma, Rare histology     

Neoadjuvant Chemotherapy in Invasive Lobular Carcinoma May Not Improve Rates of Breast Conservation

Background  Patients with invasive lobular carcinoma (ILC) experience a lower pathological complete response rate to neoadjuvant chemotherapy than patients with invasive ductal carcinoma. This study was intended to evaluate the impact of neoadjuvant chemotherapy in ILC on breast-conserving surgery (BCS) rates. Methods  Two-hundred eighty-four consecutive patients with pure ILC treated between May 1998 and September 2006 were reviewed. Surgical procedures and long-term outcomes were compared between patients receiving neoadjuvant chemotherapy and those receiving surgery first. Results  Neoadjuvant chemotherapy was administered to 84 patients; 200 patients underwent surgery first. The mean tumor size in the neoadjuvant group (4.9 cm) was significantly larger than in patients who underwent surgery first (2.5 cm, p < 0.0001). In the neoadjuvant group, clinical complete response was seen in 10% and partial response in 59%. Overall BCS rates were 17% in the neoadjuvant group compared with 43% in the surgery-first group (p < 0.0001). When controlled for initial tumor size, there was no difference (all p > 0.05) between the groups in terms of (1) the proportion of patients who underwent an initial attempt at BCS, (2) rate of failure of BCS or (3) the proportion of patients undergoing BCS as their final procedure. With a mean follow-up of 47 months, local recurrence (LR) rates were similar between the two groups (1.2% versus 0.5%, p = 0.5). Conclusion  The use of neoadjuvant chemotherapy does not increase the rates of breast conservation in patients with pure ILC.     

Lobular to Lobule: Metastatic Breast Carcinoma to Olfactory Neuroblastoma

Tumor-to-tumor metastasis (TTM) is a rare, but well-described phenomenon occurring in patients with multiple synchronous or metachronous primary malignancies. Olfactory neuroblastoma (ONB) is a rare malignant, neuroectodermal sinonasal tract tumor that occurs within the ethmoid sinus involving the cribriform plate. Very few cases of ONB have been documented to metastasize to other primary malignancies, but the reverse scenario is exceptional. During an evaluation for anosmia, a right nasal polyp was identified on imaging and endoscopy in a 66-year-old woman, with a polypectomy performed. Histologic examination showed classical features of a low-grade olfactory neuroblastoma, but within the tumor were isolated epithelioid cells which were strongly pancytokeratin immunoreactive. Review of the clinical history revealed lobular breast carcinoma treated 10 years earlier. Further evaluation with immunohistochemistry showed strong and diffuse nuclear estrogen and progesterone receptor reactivity, along with GATA3. These results confirmed TTM of an invasive lobular breast carcinoma to ONB. By employing a limited immunohistochemistry panel for all small round blue cell tumors that includes pancytokeratin, p40, S100 protein, SOX10, synaptophysin, desmin, CD99, and CD45, one is able to more accurately diagnose the classical tumor types, while also showing potentially unusual tumor features or exceptionally rare events like metastatic lobular breast carcinoma to ONB.