Nodal Positive Breast Cancer and Its Regional Lymph Node Involvement

Purpose: In breast cancer, the lymph node status is of prognostic importance and a decisive factor in therapy planning. This study shows the distribution of lymph nodes metastases of node-positive breast cancer patients. Risk factors for lymph node metastases are described.Methods: 2095 patients with primary breast cancer were analyzed. Analysis included descriptive analysis (median, standard deviation, ranges) and statistical analysis (Chi², discriminant analysis).Results: The nodal stage was positive in 39.4% of all patients and negative in 60.6%. If the nodal stage was positive, only 1 lymph node was involved in 36% of the patients; more than 1 lymph node was involved in 64% of the patients. With an increasing number of lymph node metastases in level I, the probability of an involvement in level III also increases (F 437.845, p = .000). Other indicators are evidence of hemangiosis (F 247.728, p = .000) or lymphangiosis (F 167.368, P = .000). Despite <10 affected lymph nodes, 3.4% of the patients had nodal stage N3 due to level III involvement.Conclusion: Even with only a small number of lymph node metastases in level I higher lymphatic stations are often affected. The data cannot lead to a decision regarding an operation or radiation indication, but they can better substantiate the risk for certain therapy decisions.

Real World Data of Response of Trastuzumab Based Chemotherapy in Locally Advanced HER2 Positive Breast Cancer from a Developing Country

Background: Data regarding pathologic response of Trastuzumab based chemotherapy in locally advanced HER2 positive breast cancer in neoadjuvant setting is scarce. Methods: A retrospective analysis was conducted from January 2014 to January 2019 at a tertiary cancer care centre in North India and 81 breast cancer patients who underwent neoadjuvant chemotherapy were included. The clinical and pathologic characteristics, response, toxicity and survival data was collected, collated and analyzed. Results: The most commonly observed tumor characteristics at baseline were clinical stage T4 (72.8%), nodal stage N2 (40.7%), invasive ductal carcinoma on histology (98.8%), grade 3 (66.7%) and hormone receptor negativity (54.3%). In terms of post treatment characteristics, a higher incidence of partial response (55.6%), post treatment tumor stage ypT0 (45.7%), nodal status ypN0 (54.3%), absence of extracapsular invasion (77.8%) and absence of pathologic complete response (pCR, 63%) were observed. pCR was attained in 30 patients and was most commonly associated with clinical tumor stage T4 (26/30), nodal stage N2-N3 (19/30), grade 3 (21/30) and hormone receptor negativity (20/30). Altogether, 19.75% had grade 3/4 adverse events. At 6 years, 86% v/s 61% patients were disease free (p=0.037) and 93% v/s 79% patients (p=0.181) were alive in the pCR and no pCR groups, respectively. Conclusion: Even in locally advanced breast cancer (LABC), Trastuzumab had good response in terms of pCR and survival outcomes. Thus, one can be encouraged to use this single HER2 blockade if dual blockade is not feasible in HER2 positive LABC in the neoadjuvant setting.

Tumor Size and Lobular Histology Predict for Higher Pathologic Nodal Stage Regardless of Clinical Presentation of Nodal Disease in Patients With Breast Cancer

Purpose: Omission of axillary lymph node dissection (ALND) is considered for patients with sentinel lymph node-positive (SLN+) breast cancer, but ALND remains the standard of care for clinically node-positive (cN+) patients treated with surgery first. Here, we evaluate differences in patient and tumor characteristics and pathologic nodal stage in patients with positive lymph nodes who underwent ALND. Methods: Retrospective chart review from 2010-2019 identified three groups of patients who underwent ALND for positive nodes: SLN+ (positive node identified at SLN biopsy), cNUS (abnormal preoperative US and biopsy), and cNpalp (palpable adenopathy). Patients who received neoadjuvant chemotherapy or presented with axillary recurrence were excluded. Results: Of 218 patients, 107 were SLN+, 43 were cNUS, and 68 were cNpalp. SLN+ patients compared with cNpalp were more likely to be younger (56 vs 64,p<.01), pre-menopausal (39%vs15%,p<.01), and white (62%vs37%,p<.01) with more tumors that were progesterone receptor-positive (6%vs21%,p=.02), low grade (35%vs6%,p<.01) and without lymphovascular invasion (11%vs27%,p=.02). SLN+ patients had more pN1 disease than cNUS and cNpalp (67.3% vs 39.5% vs 42.6%, p<.01). Greater tumor size and lobular histology were significantly associated with higher nodal stage in univariable regression analysis of SLN+ patients as well as a pooled analysis of the three clinical groups.Conclusion: Patient and tumor characteristics differ on either end of the nodal spectrum, with cNpalp patients having higher risk features than SLN+ patients. These higher risk features have historically resulted in ALND for patients with clinically positive nodes. However, only tumor size and histology are associated with higher pathologic nodal stage.

Negative impact of COVID-19 associated health system shutdown on patients diagnosed with colorectal cancer: a retrospective study from a large tertiary center in Ontario, Canada.

Background: In March 2020, a directive to halt all elective and non-urgent procedures was issued in Ontario, Canada because of COVID-19. The directive caused a temporary slowdown of screening programs including surveillance colonoscopies for colorectal cancer (CRC). Our goal was to determine if there was a difference in patient and tumour characteristics between CRC patients treated surgically prior to the COVID-19 directive compared to CRC patients treated after the slowdown. Methods: CRC resections collected within the Champlain catchment area of eastern Ontario in the six months prior to COVID-19 (August 1, 2019-January 31, 2020) were compared to CRC resections collected in the six months post-COVID-19 slowdown (August 1, 2020-January 31, 2021). Clinical (e.g. gender, patient age, tumour site, clinical presentation) and pathological (tumour size, tumour stage, nodal stage, lymphovascular invasion) features were evaluated using chi-square tests, T-tests and Mann-Whitney tests where appropriate. Results: 343 CRC specimens were identified (175 pre-COVID-19, 168 post-COVID-19 slowdown). CRC patients treated surgically post-COVID-19 slowdown had larger tumours (44 mm vs. 35 mm; p = 0.0048) and were more likely to have presented emergently (24% vs .10%; p < 0.001). While there was a trend towards higher tumour stage, nodal stage, and clinical stage, these differences did not reach statistical significance. Other demographic and pathologic variables including patient gender, age, and tumour site were similar between the two cohorts. Interpretation: The COVID-19 slowdown resulted in a shift in the severity of disease experienced by CRC patients in Ontario. Pandemic planning in the future should consider the long-term consequences to cancer diagnosis and management.

Predictors of Surgical Difficulty in Laparoscopic Total Mesorectal Excision

Concerns have been raised regarding the oncological safety of laparoscopic total mesorectal excision (TME) as compared to an open approach. This study aimed to identify risk factors for surgically difficult laparoscopic TME. All consecutive laparoscopic rectal cancer cases were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify risk factors for surgically difficult TME. A Surgical Difficulty Risk Score (SDRS) between 0 and 6 was calculated for each case with cases achieving an SDRS of 2 or greater being deemed as surgically difficult. A total of 2795 consecutive cases of laparoscopic TME were identified, with 464 (16.6%) surgically difficult cases. Univariate analysis found that operating in the male pelvis, performing abdomino-perineal resections, Hartmann’s procedures, and proctocolectomies were all significantly associated with higher operative difficulty (P < 0.001). A higher nodal stage of cancer (P = 0.046), and the resection of another organ (P = 0.003) were significantly associated with higher surgical difficulty. On multivariate analysis, a female pelvis was associated with a favorable laparoscopic resection (Odds ratio [OR] 0.54, 95% CI 0.43–0.67, P < 0.001), whereas patients who had another organ resection (OR 2.6, 95% CI 1.53–4.42, P < 0.001), nodal positivity (OR 1.37, 95% CI 1.11–1.69, P = 0.003), and high ASA scores had more difficult surgeries. Predictive factors for surgically difficult laparoscopic TME include male gender, high ASA scores, mid and low rectal cancer, positive nodal stage, and resection of another organ at time of surgery.

Frequency and risk factors for metastasis in newly diagnosed appendiceal carcinoma.

e16281 Background: Appendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. Methods: Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using ICD-O-3 histology/behavior codes between 2010-2015. Logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, grade, and tumor and nodal stage using the seventh edition of the American Joint Committee on Cancer (AJCC) staging system. Results: We identified a total of 3, 447 patients with known metastatic status. 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) was associated with significantly higher odds of presenting with metastasis at diagnosis in unadjusted (OR 3.55; 95% CI [2.97-4.24]) and adjusted (OR 2.97 [2.26-3.89]) regression. Signet ring cell carcinoma (SC) also had higher odds in unadjusted (OR 3.91 [2.99-5.12]) and adjusted (OR 2.05 [1.33-3.15]) regression. Goblet cell carcinoma (GC) was associated with lower odds in unadjusted (OR 0.28 [0.21-0.37]) and adjusted (OR 0.58 [0.36-0.94]) regression. The table describes the association of tumor and nodal stage with metastasis at diagnosis. Women had higher odds in unadjusted (OR 1.59 [1.39-1.82]) and adjusted (OR 1.93 [1.55-2.39]) regression. 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). Conclusions: A significant proportion of patients with appendiceal carcinoma had metastasis at diagnosis. Compared to CA, MA and SC were much more likely to present with metastasis at diagnosis, while GC was less likely. Women had almost twice the odds of presenting with metastatic disease as men. T4 and N2 stages showed much higher odds of metastasis at diagnosis compared to T1 and N0 stages, respectively. Surprisingly, T2 and T3 stages were associated with lower odds of metastasis at diagnosis than T1 stage.[Table: see text]

Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary

Purpose: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP. Methods: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. Results: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. Conclusion: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage.

Medullary breast carcinoma: a pathologic review and immunohistochemical study using tissue microarray

Introduction: Medullary breast carcinomas (MBCs) are distinguished by circumscribed, high-grade morphology with dense chronic inflammation; they are associated with the basal phenotype but have a relatively good prognosis. Methods: This study aimed to review the clinicopathological features of MBCs diagnosed at the Department of Pathology, Singapore General Hospital and correlate them with immunohistochemical expression of hormonal markers and c-erbB-2, the basal markers p53, cytokeratin (CK) 14, epidermal growth factor receptor (EGFR) and 34BE12, and the follow-up outcome. Results: Using Ridolfi’s criteria for histologic reviews, 62 patients previously diagnosed as having ‘typical MBC’ (n = 26), ‘atypical MBC’ (n = 32) and ‘invasive carcinoma with focal medullary-like features’ (n = 4) were re-classified as follows: ‘typical MBC’ (n = 6; 9.7%), ‘atypical MBC’ (n = 46; 74.2%), and ‘non-medullary infiltrating carcinoma’ (n = 10; 16.1%). Clinicopathological parameters, including ethnicity, age, tumour size and concurrent ductal carcinoma in situ (DCIS), showed no statistically significant correlation with review diagnoses and immunohistochemical findings. Presence of lymphovascular invasion and nodal stage were significantly correlated with recurrence and breast cancer-related deaths, respectively. ER negativity was significantly correlated with triple positivity for basal markers CK14, EGFR and 34BE12, which comprised patients who showed a significantly decreased disease-free survival rate within a 10–15-year follow-up period. Conclusions: Lymphovascular invasion and high nodal stage as well as triple negativity among typical and atypical MBCs that have basal-like phenotype represent a portion of invasive carcinomas with medullary features that may have poor outcomes in this otherwise relatively good prognostic group.