Lobular Carcinoma Of Breast Research Articles

HER2 positive classical type invasive breast lobular carcinoma: a clinicopathological analysis of two cases

HER2 positive classical type invasive breast lobular carcinoma: a clinicopathological analysis of two cases

Uterine fibroid metastasis as the initial manifestation of lobular breast cancer

The occurrence of breast cancer metastasis in a uterine leiomyoma is exceptional, and its diagnosis prior to detection of the primary tumor is even rarer. We describe at case of a 52-year-old female patient with a large fast growing uterine fibroid that caused pelvic pain and abdominal distention. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Histopathology of the surgical specimen showed a characteristic pattern of invasive breast lobular carcinoma in the leiomyoma. A magnetic resonance image of the breast was then performed, which reveled primary and bilateral breast cancer. She subsequently underwent neoadjuvant endocrine therapy plus cyclin inhibitors, breast-conserving surgery, and radiotherapy. To date, the patient is alive and asymptomatic after 3 years of follow-up.

Abstract C149: Relationship between PD-L1 expression and clinicopathological characteristics in Hispanic/ Latino women with breast cancer

Abstract Background: Programmed death ligand 1 (PD-L1) expression in breast cancer serves as a prognostic marker, particularly in aggressive subtypes like triple-negative breast cancer (TNBC), where it helps in predicting response to immune checkpoint inhibitors and guides immunotherapy use. Although several studies have assessed the prevalence of PD-L1 expression in breast cancer, data from the Hispanic population, especially in Latin American countries, is lacking. This study evaluates PD-L1 expression and its correlation with pathological features in Colombian women. Methods: Women with breast cancer tested for PD-L1 were selected from the archives of the Oncologic Pathology Department at the National Cancer Institute of Colombia from September 2021 to May 2024. Information from their pathology reports was extracted, and correlation analyses were carried out using Fisher's exact test Results: A total of 60 reports were screened, comprising 56 cases of ductal invasive breast carcinoma and 1 case of lobular invasive breast carcinoma. 48 individuals were tested using the PD-L1 22C3 antibody, with 41.67% of them being positive for PD-L1 expression. Among the 48 tumors tested with 22C3, 35 cases were classified as TNBC, and 13 cases corresponded to luminal B subtype with a low positive expression (1-10%) of estrogen receptors. The percentage of positive PD-L1 cases was 37.14% for TNBC and 53.85% for the luminal B subtype. Furthermore, 5 HER2-low cases were identified with 2 of them being positive for PD-L1 expression. In the correlation analyses, PD-L1 positive expression was significantly associated with a more aggressive histologic grade compared to PD-L1 negative tumors (p = 0.007). No significant association was found between PD-L1 expression and HR, HER2, or KI67 status, nor with age, necrosis, lymphovascular involvement, perineural invasion, desmoplastic response, or immune cell infiltration. Among the 12 individuals tested for PD-L1 with the SP142 antibody, none showed positive expression, precluding correlation analyses. Conclusion: This study highlights a significant association between PD-L1 expression and aggressive histologic grade in Colombian women with breast cancer. The findings underscore the potential of PD-L1 as a prognostic marker and its relevance in guiding immunotherapy in this population. Further research is needed to explore PD-L1 expression in broader Hispanic groups to better understand its clinical implications. Citation Format: Daniel Mendivelso-González, Patricia López- Correa, Nicolás Prada-Aceros, Alfredo E Romero-Rojas, Rafael Parra-Medina. Relationship between PD-L1 expression and clinicopathological characteristics in Hispanic/ Latino women with breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C149.

EP24 - Ileal metastasis masquerading as Crohn’s in lobular carcinoma of the breast, years after initial treatment- a rare case and review of literature

Abstract Gastrointestinal (GI) metastases masquerading as Crohn’s years after treated lobular carcinoma of breast is a diagnostic challenge. In some cases, the interval between the primary breast cancer and gastrointestinal metastasis is so long (3- 20 years) that the medical records for diagnosis including history might be missed. The susceptibility of invasive lobular cancer (ILC) to metastasize to gut is many times greater than invasive ductal carcinoma (IDC) (4.5% versus 0.2%, respectively). We report the case of lobular breast carcinoma metastasizing to the terminal ileum and ileocecal junction 7 years following treatment of right sided lobular breast cancer in 60 plus-year-old women. Radiological and endoscopic findings can be difficult to distinguish from inflammatory bowel disease or from primary carcinoma of the GI tract. Histopathological and immunochemistry assessments usually help in reaching the diagnosis. A high index of suspicion and awareness regarding such presentations can help in making an accurate diagnosis and subsequent treatment planning.

Double Primary Cancer: Breast Cancer and Gastric Cancer

Introduction: Breast carcinoma is the most prevalent malignancy and the second leading cause of cancer death in women, while multiple primaries are conditions where there is more than one synchronous or metachronous cancer in one individual. Double primary between breast carcinoma and colon cancer is a primary tumor with a high incidence, while breast carcinoma metastasis to the colon is a rare entity except for lobular histotype breast carcinoma. In this case report, a woman with double primary breast cancer is reported. Case Report: A 50-year-old woman came with complaints pain of the entire abdomen since 2 days before go to hospital, worsening when starting to eat, accompanied by nausea. The patient had a history of modified radical mastectomy (MRM) for indications of right breast carcinoma cT3N0M0. In addition, a history of ovarian carcinoma that had undergone chemotherapy was also found. On esophagogastroduodenoscopy examination, a gastric mass was found with ulceration and necrosis and a biopsy showed high-grade neuroendocrine carcinoma and adenocarcinoma. Conclusion: Breast malignancy can be invasive or non-invasive and can undergo metastasis. In addition to metastasis, cancer can also appear in two different places but histologically or morphologically different. This condition is called multiple primaries due to host, lifestyle, and environmental factors.

Nomograms to predict the long-term prognosis for non-metastatic invasive lobular breast carcinoma: a population-based study

Invasive lobular breast carcinoma (ILC) is one potential subset that “clinicopathologic features” can conflict with “long-term outcome” and the optimal management strategy is unknown in such discordant situations. The present study aims to predict the long-term, overall survival (OS) and cancer-specific survival (CSS) of ILC. The clinical information of patients with non-metastatic ILC was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020. A total of 31451 patients were enrolled and divided into the training cohort (n=22,017) and validation cohort (n=9434). The last follow-up was December, 31, 2020 and the median follow-up period was 99 months (1–203). Age, marriage, estrogen (ER) status, progesterone (PR) status, grade, tumor size, lymph node ratio (LNR) and combined summary (CS) stage were prognostic factors for both OS and CSS of ILC, whereas chemotherapy and radiation were independent protect factors for OS. The nomograms exhibited satisfactory discriminative ability. For the training and validation cohorts, the C-index of the OS nomogram was 0.765 (95% CI 0.762–0.768) and 0.757 (95% CI 0.747–0.767), and the C-index of the CSS nomogram were 0.812 (95% CI 0.804–0.820) and 0.813 (95% CI 0.799–0.827), respectively. Additionally, decision curve analysis (DCA) demonstrated that the nomograms had superior predictive performance than traditional American Joint Committee on Cancer (AJCC) TNM stage. The novel nomograms to predict long-term prognosis based on LNR are reliable tools to predict survival, which may assist clinicians in identifying high-risk patients and devising individual treatments for patients with ILC. Our findings should aid public health prevention strategies to reduce cancer burden. We provide two R/Shiny apps (https://ilc-survival2024.shinyapps.io/osnomogram/; https://ilc-survival2024.shinyapps.io/cssnomogram/) to visualize findings.

External auditory canal metastasis leading to peripheral facial paralysis as first manifestation of de novo stage IV invasive lobular carcinoma of the breast: a rare case report

Facial nerve (FN) palsy, as a solitary symptom resulting from a metastatic tumor, is uncommon, and metastases to the external auditory canal (EAC) are even more infrequent. In this article, we report a unique case of the de novo stage IV invasive lobular breast carcinoma (LBC) presenting as an EAC metastasis and leading to FN palsy as the first symptom, highlighting the importance of considering a broad differential diagnosis.

Automated feathered edge blood smear analysis: early diagnosis of carcinocythemia in a case of disseminated intravascular coagulation with multi-organ failure.

Carcinocythemia, known as the presence of circulating tumor cells in the peripheral blood, is difficult to detect when the carcinoma cells are minimally present. We describe a case of a 56-year-old patient presenting with disseminatedintravascular coagulation (DIC) and multiple organ failure. Despite initial suspicion of sepsis, a peripheral blood smear showed the presence of atypical cells, mainly located at the feathered edge, leading to a presumptive diagnosis of carcinocythemia of unknown primary origin. The presence of a high-fluorescent cell population detected by our hematology analyzer (Sysmex XN-9100) and immunohistochemical staining with pancytokeratin AE1/AE3 confirmed the carcinoma cell origin. The patient died 4 days after referral to our hospital. Postmortem examination revealed a pleomorphic lobular breast carcinoma (triple-negative, androgen receptor-negative). Given the clinical acuity of patients with carcinocythemia, early diagnosis is essential to guide management. This case underscores the importance of optimizing current workflows relying on complex flagging algorithms and enhanced digital imaging to aid in the early detection of such rare condition. When patients present with DIC of unknown origin and high fluorescent signals are detected on the hematology analyzer, carcinocythemia should actively be ruled out by extensive microscopic peripheral blood examination.

A histomorphological and immunohistochemical analysis of invasive lobular carcinoma of breast: A case series

Invasive lobular carcinoma (ILC) is the second most common special subtype of invasive breast carcinoma comprising 5–15%. ILC defines as invasive carcinoma comprising non-cohesive single-file linear pattern in fibrous stroma. The aim of the study was to evaluate the histomorphological features and immunohistochemical analysis of ILC. A total of 19 cases were encountered from March 2020 to February 2024 out of 129 breast cancers. The sociodemographic profiles and clinicopathological parameters of the patients were studied with special emphasis on their morphology and hormone receptor status. The mean age of patients is 42.8 years. Out of 19 cases, 84.2% showed feature of classic type, 5.2% of tubule-lobular, and 10.5% of pleomorphic lobular carcinoma. The majority of cases (63.2%) showed histologic Grade 2, and 10.5% showed Grade 3. On immunohistochemistry examination, 79% were estrogen receptor (ER) and progesterone receptor (PR) positive with 10.5% of cases was human epidermal growth factor receptor 2/neu (HER2/neu) positive. Our study showed higher cases of classic type ILC, mostly of histologic Grade 2; higher ER-PR receptor positivity and HER2/neu negativity.

Gastrointestinal Metastases From Lobular Breast Carcinoma: A Literature Review.

Invasive lobular carcinoma (ILC) represents a rare subtype of breast carcinoma, originating from the lobule. Unlike ductal carcinoma, ILC does not express E-cadherin and thus can metastasize to uncommon sites. We aimed to investigate the clinicopathological characteristics of the rare subgroup of ILC patients with gastrointestinal (GI) metastases. A PubMed search was undertaken using the terms "Lobular Breast Carcinoma" AND "Gastrointestinal Metastasis." We identified 169 cases, with metachronous GI metastatic disease being approximately twice as common as synchronous GI metastases. The median age at initial diagnosis was 56.7 years (24-88). The majority of patients were hormonal receptor-positive and only a small minority was HER2-positive. The appearance of a gastrointestinal lesion was often the mode of revelation of ILC. Differential diagnosis from primary gastrointestinal cancer is sometimes challenging, especially in the case of signet-ring cell carcinoma. The median time from breast cancer diagnosis to GI metastases was 6.5 years (0-33). Most common metastatic sites include the stomach, colon, and rectum, in order of decreasing frequency, whereas metastases were found in every part of the digestive tract. In conclusion, metastases of ILC can arise in the gastrointestinal tract and they should be managed similarly to metastatic breast cancer.

Prospective investigation of amino acid transport and PSMA-targeted positron emission tomography for metastatic lobular breast carcinoma.

To explore the feasibility of imaging amino-acid transport and PSMA molecular pathways in the detection of metastatic breast invasive lobular carcinoma (ILC) and if there is superior detection compared to standard-of-care imaging [computed tomography (CT)/bone scan, or 18F-FDG positron-emission-tomography (PET)-CT]. 20 women with de-novo or suspected metastatic ILC underwent two PET-CT scans with 18F-fluciclovine and 68Ga-PSMA-11 on separate days. Uptake per patient and in 3 regions per patient - ipsilateral axillary lymph node (LN), extra-axillary LN (ipsilateral supraclavicular or internal mammary), or distant sites of disease - was compared to standard-of-care imaging (CT/bone scan in 13 patients and 18F-FDG PET-CT in 7 patients). Results were correlated to a composite standard of truth. Confirmed detection rate (cDR) was compared using McNemar's test. Mean SUVmax of 18F-fluciclovine and 68Ga-PSMA-11 in the most avid lesion for each true positive metastatic region and intact primary lesion were compared by t-test. The cDR for standard-of-care imaging was 5/20 patients in 5/60 regions. 68Ga-PSMA-11 PET-CT detected metastasis in 7/20 patients in 7/60 regions. 18F-fluciclovine PET-CT detected metastasis in 9/20 patients in 12/60 regions. The cDR for 18F-fluciclovine PET-CT was significantly higher versus standard-of-care imaging on the patient and combined region levels, while there were no significant differences between 68Ga-PSMA-11 and standard-of care imaging. 18F-fluciclovine cDR was also significantly higher than 68Ga-PSMA-11 on the combined region level. Mean SUVmax for true positive metastatic and primary lesions with 18F-fluciclovine (n = 18) was significantly greater than for 68Ga-PSMA-11 (n = 11) [5.5 ± 1.8 versus 3.5 ± 2.7 respectively, p = 0.021]. In this exploratory trial, 18F-fluciclovine PET-CT has a significantly higher cDR for ILC metastases compared to standard-of-care imaging and to 68Ga-PSMA-11. Mean SUVmax for true positive malignancy was significantly higher with 18F-fluciclovine than for 68Ga-PSMA-11. Exploratory data from this trial suggests that molecular imaging of amino acid metabolism in patients with ILC deserves further study. Early phase (I-II) clinical trial (NCT04750473) funded by the National Institutes of Health (R21CA256280).

Gastric metastasis and peritoneal carcinosis revealing primary breast cancer: an unusual presentation.

Breast cancer is the most frequent cancer among women. Gastrointestinal tract metastases are uncommon and might be misidentified as primary carcinoma.A noteworthy case-study involved 53-year-old-woman complaining from epigastric pain, ascites and overall health decline. Initial investigations were inconclusive, prompting laparoscopic peritoneal biopsies which revealed independent cell proliferation. Subsequently, a second look upper digestive endoscopy showed multiple gastric ulcerations suggestive of gastric carcinoma. Histologic examination confirmed independent cell proliferation with estrogen receptors expression, a characteristic feature of breast carcinoma. Further investigations led to bilateral invasive lobular breast carcinoma diagnosis. Epirubicin cycophosphamide was prescribed after progression under letrozole ribocilib therapy.This case aims to raise awareness among clinicians about the importance of ruling out breast cancer in patients with peritoneal carcinosis and paying attention to digestive symptoms in breast cancer patients with careful gastric endoscopic examination to avoid misdiagnosis.

Everolimus for advanced breast cancer: Is the histological subtype important?

e13165 Background: Invasive lobular (L) breast carcinomas (BC), which account for up to 15% of all BC, had particularly histopathological characteristics: tends to be estrogen/progesterone receptor positive and HER2-neu negative and as such are treated with endocrine therapy (ET). It had been demonstrated a frequent activation of PI3K–AKT–mTOR signaling in LBCs, suggesting this pathway to be a promising therapeutic target for LBC. Interestingly, in some of these patients, the subsequent use of a mTOR inhibitor (everolimus) combined with an ET produced greater clinical benefits. Our aim is to evaluate the efficacy of everolimus in advanced BC (ABC) in the usual clinical practice, focusing on LBC. Methods: We retrospectively analyzed 147 women with ABC from four Spanish hospitals who were treated with everolimus (Ev) in second or successive lines of treatment between 2014-2023. We performed a descriptive statistical analysis of the clinicopathological variables and calculated the investigator-assessed time to treatment failure (TTF), defined as the interval from initiation of treatment to its premature discontinuation (because of progression disease (PD) or toxicity), as well as its association using Kaplan-Meier test. Survival curves were analyzed using long-rank test. Finally, we analyzed the subgroup of those with everolimus TTF (TTF2) longer than previous line TTF (TTF1) by Xi2 test. Results: With a median (m) age of 59, 21 (14%) patients (pts) were diagnosed with advanced LBC. The histopathological characteristics of the pts are shown (Table). Treatment had to be stopped in 24 pts due to toxicity (oral mucositis 21%), and the rest was due to PD or exitus. The response rate (stabilization, partial and complete response (CR)) was 49% with 4% of CR. The overall m of TTF2 was 9,1 months, while the TTF1 m was 9,5 months. Analyzing by histology, TTF2 m was 18.16 months in LBC vs 7.85 in ductal BC (p=0.01). Contrary to expectations, 40 pts (27,2%) had a longer TTF2 compared with TTF1 (p>0.001). When analyzing this subgroup we found 9 pts with LBC and 27 DBC (p>0,05). 26 pts (65%) had not received previous line with HT (p=0.005). On the other hand, when analyzing the subgroup of pts with LBC, up to 47.36% of pts had TTF2>TTF1. Conclusions: The use of everolimus in pts with LBC appears to be more effective than in DBC according to the results reported in our series and its use in initial hormonal lines may be reconsidered. However, we need more prospective studies differentiating histologies to demonstrate our results for others Pi3k inhibitors. [Table: see text]

Once-daily upadacitinib versus placebo in adults with extensive non-segmental vitiligo: a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study

Janus kinase (JAK) inhibition is a promising approach for treating vitiligo. We aimed to assess the efficacy and safety of upadacitinib, an oral selective JAK inhibitor, in adults with non-segmental vitiligo. This was a phase 2, multicentre, randomised, double-blind, placebo-controlled, dose-ranging study completed at 33 clinical centres in the United States, Canada, France, and Japan. Eligible patients were aged 18-65 years with non-segmental vitiligo and had a Facial Vitiligo Area Scoring Index (F-VASI) ≥0.5 and a Total Vitiligo Area Scoring Index (T-VASI) ≥5. Patients were randomly assigned (2:2:2:1:1) using an interactive response technology to receive upadacitinib 6mg (UPA6), upadacitinib 11mg (UPA11), upadacitinib 22mg (UPA22), or placebo (PBO; preassigned to switch to either UPA11 or UPA22 in period 2) once daily for 24 weeks (period 1). For weeks 24-52 (period 2), patients randomly assigned to upadacitinib continued their treatment, and patients receiving PBO switched to their preassigned upadacitinib dose in a blinded fashion. The primary endpoint was the percent change from baseline in F-VASI at week 24. Efficacy was analysed in the intention-to-treat population, and safety was examined in all randomly assigned patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT04927975. Between June 16, 2021, and June 27, 2022, 185 patients (including 115 [62%] who were female and 70 [38%] who were male) were randomly assigned to UPA6 (n=49), UPA11 (n=47), UPA22 (n=43), or PBO (n=46). At week 24, the LS mean difference versus PBO in the percent change from baseline in F-VASI was-7.60 (95% CI-22.18 to 6.97; p=0.3037) for UPA6,-21.27 (95% CI-36.02 to-6.52; p=0.0051) for UPA11, and-19.60 (95% CI-35.04 to-4.16; p=0.0132) for UPA22. The LS mean difference versus PBO in the percent change from baseline in T-VASI was-7.45 (95% CI-16.86 to 1.96; p=0.1198) for UPA6,-10.84 (95% CI-20.37 to-1.32; p=0.0259) for UPA11 and-14.27 (95% CI-24.24 to-4.30; p=0.0053) for UPA22. Ongoing treatment with upadacitinib induced continuous skin repigmentation over time without reaching a plateau through week 52. The rates for study drug discontinuation and serious treatment-emergent adverse events (TEAEs) were higher in the UPA22 group than in the UPA11 and UPA6 groups. Eight serious TEAEs, including one death of unknown cause and one case of infiltrating lobular breast carcinoma, were reported through 52 weeks; only two serious TEAEs (coronary artery arteriosclerosis [UPA6 (n=1)] and non-fatal ischemic stroke [UPA11 (n=1)]) were deemed by the investigator to have a reasonable possibility of being related to study drug. The one case of breast cancer in the UPA11 group was deemed unrelated to study drug, and the one death of unknown cause in the UPA22 group was reviewed and adjudicated and was deemed to be unrelated to study drug. The most common TEAEs were COVID-19, headache, acne, and fatigue. No new safety signals were observed. Upadacitinib monotherapy led to substantial repigmentation of both facial and total body vitiligo lesions and may offer an effective treatment option for adults with extensive non-segmental vitiligo. Based on these findings, upadacitinib 15mg is being investigated in adults and adolescents with non-segmental vitiligo in an ongoing phase 3 randomised controlled trial. AbbVie Inc.

Recurrence in lobular carcinoma of the breast: A 14-year review.

The two most common types of breast cancer are invasive or infiltrating ductal carcinoma (IDC) and invasive or infiltrating lobular carcinoma (ILC) (Pestalozzi etal., J. Clin. Oncol., 26, 2008, 3006). Between 5% and 15% of invasive breast carcinomas are lobular carcinomas (Pestalozzi etal., J. Clin. Oncol., 26, 2008, 3006; Dossus and Benusiglio, Breast Cancer Res., 17, 2015, 37; Braunstein etal., Breast Cancer Res. Treat., 149, 2015, 555). The paucity of data relating to recurrence rates of lobular cancers prompted this study. A retrospective cohort study of all cases of lobular breast carcinoma reported to the Western Australia Cancer Registry with the clinical and pathological details between 2000 and 2014. Overall, 2463 subjects with a total of 2526 events of invasive lobular carcinoma of the breast. 11/2463 (0.45%) subjects met criteria for local recurrence of invasive lobular breast cancer, with an incidence of 1 in 224. There are clinical implications for the management and follow-up for patients with a diagnosis of lobular cancer of the breast. Due to the low recurrence rate, now, the standard practice in our institution does not offer magnetic resonance imaging (MRI) as part of the follow-up for ILC patients. Other centres should establish local recurrence rates to aid development of appropriate management protocols.

CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation

The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region. Few studies employing quantitative methods and covering CpG island shores, regions of relatively low CpG density situated proximal to conventional promoter CpGs, have been conducted, revealing lower percentages of methylation ranging from 0 to 51%. Therefore, using the quantitative pyrosequencing method, we examined CDH1 methylation in the island region and shores in E-cadherin deficient ILC cases (15 with CDH1 mutation and 22 non-mutated), 19 cases of invasive breast carcinomas non-special type (IBC-NSTs), and five cases of usual ductal hyperplasia (UDH). Our analysis revealed CDH1 methylation frequencies ranging from 3 to 64%, with no significant increase in methylation levels in any group of ILCs (median = 12%) compared to IBC-NST (median = 15%). In addition, considering the poorly studied association between the number of tumor-infiltrating lymphocytes (TILs) and CDH1 methylation in breast cancer, we undertook a thorough analysis within our dataset. Our findings revealed a positive correlation between CDH1 methylation and the presence of TILs (r = 0.5; p-value < 0.05), shedding light on an aspect of breast cancer biology warranting further investigation. These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in gene methylation.

Abstract PO5-02-13: Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma

Abstract Purpose Invasive lobular carcinoma (ILC) is the second common types of breast cancer and its clinicopathological feature and outcomes differ from invasive ductal carcinoma (IDC). However, in terms of survival outcomes, there are conflicting data on the prognostic implication of the ILC when compared to that of IDC. This study aims to evaluate the survival outcomes of patients diagnosed with ILC at single center and compared them with those of IDC. Methods We reviewed the data of the 13,034 IDC patients and 935 ILC patients who were treated between January 2005 and December 2022 at Seoul National University Hospital. We investigated the overall treatment outcomes of two histologic types with a special focus on the tumor size and lymph nodes. Result ILC exhibited distinct characteristics compared to IDC, including a larger tumor size (2.6 ± 1.8 vs. 1.9 ± 1.1 cm, p &amp;lt; 0.001) and a higher hormone receptor positivity (97.4% vs. 79.3%, p &amp;lt; 0.001). Additionally, the presence of lymphovascular emboli was lower in ILC (8.0% vs. 24.6%, p &amp;lt; 0.001). While IDC patients showed slightly better overall survival (OS) than ILC (10-year OS, ILC 89.9% vs. IDC 91.1%, the difference was not statistically significant (p = 0.85). However, distant metastasis-free survival (DMFS) was significantly higher in ILC (10-year DMFS, ILC 93.2% vs. IDC 89.9%, p = 0.001). Age at diagnosis, tumor size, presence of lymphovascular emboli, high expression of Ki-67, and higher pathologic N stage were poor prognostic markers for ILC. Multivariate analysis for DMFS showed that age, high expression of Ki-67 and higher pathologic N stage were poor prognostic markers for ILC. Tumor size was not an independent prognostic factor for DMFS (HR: 0.92, 95% CI: 0.72-1.17, p = 0.491) and for OS (HR: 1.18, 95% CI: 0.99-1.41, p = 0.060) in ILC. Conclusion Our data suggest that the tumor size, which is a well-known prognostic factor in IDC, carries distinctly different prognostic implication in ILC. These observation indicate that adjuvant treatment decisions based on tumor size can be tailored to different histologic subtypes of breast cancer. Citation Format: Ik Beom Shin, Eunhye Kang, Ji-Jung Jung, Hawjeong Lee, Jin Young Byeon, Yunhee Choi, Changjin Lim, Jong-Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-13.

Abstract PO5-20-10: Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis

Abstract Background: Symptomatic bone marrow metastasis causing myelophthisis is a rare manifestation of metastatic breast cancer, indicating a poor prognosis due to significant cytopenias. CDK4/6 inhibitors are first-line therapies for metastatic hormone-positive breast cancer but remain an unclear choice in breast cancer patients with significant cytopenias due to associated hematological adverse effects. We present a case of biopsy-proven hormone-positive breast cancer with bone marrow infiltration causing profound pancytopenia. CDK4/6 inhibitors were safely administered despite their cytopenic effects. Case Presentation: A 59-year-old female presented after an abnormal annual mammogram and biopsy showed calcifications stromal fibrosis, cyst formation, and usual ductal hyperplasia in the right upper outer quadrant. One month later, she presented to an outside hospital with gingival bleeding, epistaxis, progressive dyspnea on exertion, and generalized weakness. Labs showed severe anemia with a hemoglobin of 4.8 g/dL (baseline 12.1 g/dL), thrombocytopenia with platelets of 5 K/mm (baseline 215 K/mm), LDH of 879, reticulocyte count of 5%, and negative direct Coombs test. Peripheral smear showed no schistocytes, but showed nucleated RBCs, severely reduced platelets, and occasional giant platelets. The patient was treated for presumed ITP, and the presence of nucleated RBCs prompted bone marrow biopsy which confirmed metastatic invasive lobular carcinoma breast cancer (ER 90-95%, PR 90-95%, HER2 1+). She was discharged on letrozole 2.5 mg daily with close outpatient oncologic follow-up. One week later, she presented to our institution with persistent symptomatic anemia and thrombocytopenia. Inpatient systemic therapy was begun using dose-reduced Palbociclib (75mg) and letrozole with close CBC monitoring while also receiving packed red blood cells (goal &amp;gt;6.5) and platelet transfusions (goal &amp;gt;10). Repeat bone marrow biopsy showed extensive marrow fibrosis, but no significant hematopoietic elements. ADAMTS13 was 134%, ruling out TTP, and she was treated again for presumed ITP with dexamethasone and IVIG, Throughout the 4-week admission, her right breast mass decreased in size and she was discharged after completing 3 weeks of Palbociclib with biweekly outpatient transfusions. During follow-up, the patient’s hemoglobin and platelets slowly started to respond allowing her to become transfusion-independent and allowing dose escalation. Restaging scans 2 months after hospitalization showed an overall improvement of disease burden. The patient continued to do well for almost 18 months, however, later redeveloped visceral crisis and is responding to chemotherapy. Discussion: There is limited data on the management of breast cancer with bone marrow infiltration at presentation. A wide range of survival data in different case reports exists, ranging from 5 to 44 months. However, chemotherapy was used in these studies rather than CDK4/6 inhibitors. By far, cytopenias are the most concerning grade 3 and 4 side effect of Palbociclib. Data from the PALOMA-1 trial suggest that hematologic toxicities, specifically neutropenia, were different from those associated with cytotoxic chemotherapies and are more transient and reversible in nature. Studies have examined the in vitro mechanism of bone marrow suppression in Palbociclib versus cytotoxic chemotherapy, and its cytostatic effect on neutrophil precursors allows for hematological toxicities to be transient. With strong supportive care measures, patients in bone marrow visceral crisis can be safely treated with cytopenic CDK4/6 inhibitors. Citation Format: Nikita Dahake, Jordan Senchak, Jalil Nasibli, Jason Incorvati. Treatment with CDK4/6 Inhibitor in a Patient with Metastatic Breast Cancer Causing Myelophthisis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-20-10.

Differences in Histological Subtypes of Invasive Lobular Breast Carcinoma According to Immunohistochemical Molecular Classification.

The aim of this study was to compare the differences between histological and molecular subtypes of invasive lobular carcinoma (ILC) of the breast, in order to be able to predict the behavior and prognosis of the disease, as well as to effectively determine therapy. This study included 263 cases of breast ILC diagnosed over a seven-year period. The diagnosis of invasive lobular carcinoma is based on the characteristic growth pattern and phenotype of cancer cells with the respective subtypes: classic, alveolar, solid, tubulolobular, pleomorphic and mixed lobular type. The examined cases were divided into five groups according to molecular classification based on the expression of ER, PR, HER2 and Ki67 immunohistochemical markers. It was found that the pleomorphic subtype occurred statistically significantly less often as the luminal A subtype compared to others (p = 0.00027), and the HER2-enriched subtype occurred statistically significantly more often in the pT4 stage (p = 0.024). The results of this study significantly singled out the luminal A subtype, and among them classic ILC, as the subtype with the most favorable expression ratio of the investigated predictive/prognostic immunohistochemical markers.

Comparison of Clinicopathological Features of Pleomorphic and Invasive Lobular Breast Carcinomas.

Accounting for about 15% of invasive lobular carcinomas and 1% of breast carcinomas, pleomorphic lobular carcinoma is known to be a rare histological subtype of invasive lobular carcinoma. Yet, it is more aggressive and produces a worse prognosis than other breast cancers. Ultimately, the present study compares the clinicopathological features of pleomorphic and invasive lobular breast carcinomas. In the study, we retrospectively evaluated the data of 262 patients with histological subtypes of classical and pleomorphic lobular cancers having been recruited for surgical operations. After resorting to Kolmogorov-Smirnov and Shapiro-Wilk tests to check the normality of distribution, the categorical and continuous variables were compared between the groups using the chi-square test and independent samples t test, respectively. In all analyses, we considered a P-value of <.05 to be statistically significant. Our findings revealed that the groups with lobular and pleomorphic groups significantly differed by Ki-67 value, estrogen receptor negativity, grade, multicentricity, multifocality, surgical margin positivity, completion mastectomy, and metachronous contralateral tumor (P < .05). We discovered that pleomorphic type was associated with higher grades, estrogen receptor negativity, and Ki-67 expression. The incidence of metachronous breast cancer was high in the pleomorphic group, which may be a noteworthy finding to be considered in follow-ups. In addition, the high rates of multicentricity and multifocality of tumors in the pleomorphic group may be associated with increased surgical margin positivity and a higher likelihood of mastectomy. In a nutshell, our findings may guide patients and surgeons regarding the type of intervention and reconstruction options to be adopted in prospective surgeries.