Characteristics and risk factors of axillary lymph node metastasis of microinvasive breast cancer.

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.

Clinical significance of microinvasive breast cancer across the different subtypes and human epidermal growth factor receptor 2 expression levels.

PURPOSE: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC. METHODS: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC). RESULTS: When divided into four subtypes, hormone receptor (HR)+/HER2-, HR+ /HER2+ , HR-/HER2+ , and HR-/HER2-, HR-/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0-271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR-/HER2+ group. The five-year DFS for the HR-/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2- group (p = 0.024 The five-year LRFS for HER2- patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR-/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2- group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412-3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408-7.953, p = 0.006 adjusted). CONCLUSION: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients.

Characteristics of Microinvasive Ductal Carcinoma In Situ Versus Noninvasive and Invasive Breast Cancer.

BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS. METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence. CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.

Sentinel and non-sentinel lymph node metastases in patients with microinvasive breast cancer: a nationwide study.

PURPOSE: To determine the incidence and risk factors of sentinel lymph node (SN) and non-SN metastases in patients with microinvasive breast cancer (MIBC, T1mic). This to identify MIBC patients in whom axillary staging can be safely omitted. METHODS: The Danish Breast Cancer Group database was used to identify a total of 409 women with breast cancer ≤ 1 mm who underwent sentinel lymph node biopsy (SLNB) between 2002 and 2015. After validation, 233 patients were eligible for the analysis. The incidence rates of SN and non-SN metastases were determined. The associations between clinicopathological variables and a positive SN [pN1, pN1mi, or pN0(i+)] were analyzed using univariate and multivariate designs. RESULTS: Of 233 patients with MIBC, only 9 (3.9%) had SN macrometastases. An additional 18 (7.7%) and 23 (9.9%) had SN micrometastases and isolated tumor cells (ITCs), respectively. Of patients with SN macrometastases, two (22.2%) had non-SN macrometastases. In the adjusted analysis, a positive SN was associated with younger age (P = 0.0001) and a positive human epidermal growth factor 2 receptor (HER2) status (P = 0.03). CONCLUSIONS: The low incidence of SN macrometastases < 4% suggests omission of axillary staging in MIBC patients without staging at primary surgery, especially in older (≥ 50 years) HER2- patients. Still, the relatively high proportion of patients with non-SN macrometastases indicates that axillary treatment might be considered in SN positive patients, especially in younger HER2+ MIBC patients.

Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial.

PURPOSE: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. METHODS: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. RESULTS: Median follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77). CONCLUSIONS: The risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer.

Ductal Carcinoma In Situ (DCIS) and Microinvasive DCIS: Role of Surgery in Early Diagnosis of Breast Cancer.

Advances in treatments, screening, and awareness have led to continually decreasing breast cancer-related mortality rates in the past decades. This achievement is coupled with early breast cancer diagnosis. Ductal carcinoma in situ (DCIS) and microinvasive breast cancer have increasingly been diagnosed in the context of mammographic screening. Clinical management of DCIS is heterogenous, and the clinical significance of microinvasion in DCIS remains elusive, although microinvasive DCIS (DCIS-Mi) is distinct from "pure" DCIS. Upfront surgery has a fundamental role in the overall treatment of these breast diseases. The growing number of screen-detected DCIS diagnoses with clinicopathological features of low risk for local recurrence (LR) allows more conservative surgical options, followed by personalised adjuvant radiotherapy plans. Furthermore, studies are underway to evaluate the validity of surgery omission in selected low-risk categories. Nevertheless, the management, the priority of axillary surgical staging, and the prognosis of DCIS-Mi remain the subject of debate, demonstrating how the paucity of data still necessitates adequate studies to provide conclusive guidelines. The current scientific scenario for DCIS and DCIS-Mi surgical approach consists of highly controversial and diversified sources, which this narrative review will delineate and clarify.

Relationship between the changes of positivity rate of HER2 expression and the diameter of invasive lesions in early breast cancer and its clinical significance.

BACKGROUND: The expression status of HER2 is an important factor in evaluating the prognosis of breast cancer. We found that the positivity rate of HER2 varied with the diameter of invasive lesions in early breast cancer.We aimed to explore the relationship between the change of HER2 positivity rate of early breast cancer and the diameter of the invasive foci and its clinical significance. METHODS: A total of 217 patients with microinvasive breast cancer and T1a stage breast cancer were enrolled in this study. Machine learning algorithm was used to extract morphological features of invasive lesions in early breast cancer. Using Spearman to analysis the clinicopathological and morphological features related to HER2 expression McNemar test was used to analyze the consistency of HER2 expression between the carcinoma in situ area and the invasive cancer area. RESULTS: In early breast cancer, the diameter of the invasive foci was strongly negatively correlated with the expression status of HER2 (rho=-0.468, p < 0.001). As the diameter of the invasive foci increases, the HER2 positivity rate gradually decreases. When the diameter of the invasive foci> 2 mm, the positivity rate of HER2 was significantly reduced (from 52.6% to 16.1%, p < 0.001), which was close to the positivity rate of HER2 in ordinary invasive breast cancer. Moreover, most of the clinicopathological characteristics of breast cancer with an invasive lesion diameter of 1-2 mm and DCIS-MI were not significantly different (p > 0.05). Among 217 patients, the consistency rate of HER2 expression in carcinoma in situ and invasive foci areas was 97.7% (212/217), and there was no significant difference in HER2 expression status (p = 0.25 and p = 0.50, respectively). CONCLUSIONS: We recommend that breast cancer with an invasive lesion diameter of 1-2 mm should be classified as microinvasive breast cancer. In early breast cancer,the expression status of HER2 in the invasive foci area can refer to the HER2 expression status in carcinoma in situ area. However, it needs further support from a large amount of data and follow-up results.

Regional Lymph Node Metastasis and Axillary Surgery of Microinvasive Breast Cancer: A Population-Based Study.

Microinvasive breast cancer (MBC for short) is a rare entity with the decision of axillary surgery under debate in clinical practice. We aimed to unravel the lymph node metastasis (LNM) rate, axillary surgery, and prognosis of MBC based on 11,692 patients derived from the Surveillance Epidemiology and End Results (SEER) database between 2003 and 2015. In this retrospective study, 19.5% (2276/11,692) of patients received axillary lymph node dissection (ALND), 80.5% (9416/11,692) received non-ALND. In the total cohort, 10-year breast cancer-specific survival (BCSS) was 96.3%, and the LNM rate was 6.4% (754/11,692). Multivariate analyses showed that LNM had the strongest predictive weight (N3, HR 14.200, 95% CI 7.933−25.417; N2, HR 12.945, 95% CI 7.725−21.694; N1, HR 3.05, 95% CI 2.246−4.140, all p < 0.001). Kaplan−Meier analyses showed that ALND did not confer a survival benefit on 10-year BCS in patients with N0 (94.7% vs. 97.1%, p < 0.001) and in patients with 1−2 positive nodes (92.1% vs. 89.5%, p = 0.355), respectively, when compared to non-ALND. Our study demonstrated that the vast majority of MBC have a low LNM rate and excellent prognosis; patients with LNM showed poor prognosis. Assessment of lymph node status is necessary, and non-ALND surgery is required and sufficient for MBC with 0−2 positive nodes.

Microinvasive breast carcinoma: An analysis from ten Senonetwork Italia breast centres.

BACKGROUND AND OBJECTIVES: We studied a large series of ductal carcinoma in situ with microinvasion (MIDC) an infrequent disease whose diagnosis and management are not well defined. METHODS: 17,431 cases of breast carcinoma were treated between 2011 and 2016 by ten Italian Breast Units. Our analysis included diagnostic and clinic-pathological characteristics, surgical management, and the use of adjuvant therapies. RESULTS: 15,091 cases (86.6%) were infiltrating carcinomas (IC), 2107 (12.1%) ductal carcinoma in situ (DCIS), and 233 (1.3%) MIDC. Age at diagnosis did not differ between DCIS and MIDC. MIDC were usually larger and expressed more frequently biologically aggressive features (higher Ki67 values, hormone receptor negativity and HER2/neu over-expression) (p < 0.01). Axillary lymph nodes were involved in 25 MIDC cases (12%), but >3 lymph nodes were involved in two cases only (1%). At multivariable analysis, only lymphovascular invasion (LVI) was associated with lymph node status (p < 0.01). Hormone therapy was prescribed in 388/1462 DCIS cases (26.5%), in 84/200 MIDC cases (42%), and in 11,086/14,188 IC cases (84.7%) (p < 0.01). Chemotherapy was administered in 28/190 MIDC cases (14.7%), and in 4080/11,548 IC cases (35.3%) (p < 0.001). CONCLUSIONS: This is one of the largest studies of MIDC reported in the literature. Approximately 10% of DCIS harbor one or more foci of MIDC, and the latter often expresses aggressive biological features. LVI is a predictor of axillary node involvement, but this is infrequent and usually limited. Conservative surgery is performed less often than in DCIS, and adjuvant chemotherapy is less frequently utilized compared to IC.

Is adjuvant chemotherapy necessary for patients with microinvasive breast cancer after surgery?

OBJECTIVE: Survival and treatment of patients with microinvasive breast cancer (MIBC) remain controversial. In this paper, we evaluated whether adjuvant chemotherapy is necessary for patients with MIBC to identify risk factors influencing its prognosis and decide the indication for adjuvant chemotherapy. METHODS: In this retrospective study, 108 patients with MIBC were recruited according to seventh edition of the staging manual of the American Joint Committee on Cancer (AJCC). The subjects were divided into chemotherapy and non-chemotherapy groups. We compared the 5-year disease-free survival (DFS) and overall survival (OS) rates between groups. Furthermore, we analyzed the factors related to prognosis for patients with MIBC using univariate and multivariate analyses. We also evaluated the impact of adjuvant chemotherapy on the prognostic factors by subgroup analysis after median follow-up time of 33 months (13-104 months). RESULTS: The 5-year DFS and OS rates for the chemotherapy group were 93.7% and 97.5%, whereas those for the non-chemotherapy group were 89.7% and 100%. RESULTS indicate that 5-year DFS was superior, but OS was inferior, in the former group compared with the latter group. However, no statistical significance was observed in the 5-year DFS (P=0.223) or OS (P=0.530) rate of the two groups. Most relevant poor-prognostic factors were Ki-67 overexpression and negative hormonal receptors. Cumulative survival was 98.2% vs. 86.5% between low Ki-67 (≤20%) and high Ki-67 (>20%). The hazard ratio of patients with high Ki-67 was 16.585 [95% confidence interval (CI), 1.969-139.724; P=0.010]. Meanwhile, ER(-)/PR(-) patients with MIBC had cumulative survival of 79.3% compared with 97.5% for ER(+) or PR(+) patients with MIBC. The hazard ratio for ER(-)/PR(-) patients with MIBC was 19.149 (95% CI, 3.702-99.057; P<0.001). Subgroup analysis showed that chemotherapy could improve the outcomes of ER(-)/PR(-) patients (P=0.014), but not those who overexpress Ki-67 (P=0.105). CONCLUSIONS: Patients with MIBC who overexpress Ki-67 and with negative hormonal receptors have relatively substantial risk of relapse within the first five years after surgery. However, adjuvant chemotherapy can only improve the outcomes of ER(-)/PR(-) patients, but not those who overexpress Ki-67. Further studies with prolonged follow-up of large cohorts are recommended to assess the prognostic significance and treatment of this lesion.

Microinvasive breast cancer: pathological parameters, cancer subtypes distribution, and correlation with axillary lymph nodes invasion. Results of a large single-institution series.

BACKGROUND: Microinvasive breast cancer is a rare entity in which an invasive component not exceeding 1 mm is found, mostly in a ductal carcinoma in situ setting. Its diagnosis can be difficult and must rely upon immunohistochemistry markers. Many studies have analyzed pathological characteristics of this cancer to delineate its biological profile and possibly identify risk factors of axillary lymph nodes infiltration, which might be present and therefore clinically relevant. Starting from a relative large number of cases we aimed to analyze pathological data, cancer subtypes distribution, and their correlation to nodal metastasis, comparing our results to the existing recent literature. METHODS: All cases of microinvasive breast cancer were retrieved from institutional database from 1992 to 2014. Pathological parameters were analyzed for entire cohort. Moreover, cases submitted to standardized sentinel node biopsy in a restricted period, 2000-2014, were selected to correlate pathology and cancer subtype to axillary lymph nodes status. RESULTS: 174 cases (1.4 % of operated breast cancers) were evaluated in the larger period, 1992-2014. Neither specific pathological parameters were expressed nor a peculiar cancer subtype was represented. 126 cases were selected for axillary staging analysis. Eighteen cases (14.3 %) had lymph nodes metastasis, 10 ITCs (7.9 %), 3 micrometastases (2.4 %), and 5 macrometastases (4 %). An associated intraductal component of carcinoma over 20 mm in maximum dimension resulted significant at multivariate analysis, but only if including ITCs, while this risk factor was not reproduced for micro- and macrometastases only. CONCLUSIONS: Microinvasive breast cancer does not seem to have specific pathological and biological traits. An associated intraductal component of carcinoma >20 mm in size is a specific risk factor for ITCs nodal metastasis. Its clinical significance is anyway limited and therefore sentinel node biopsy should be performed case by case and not routinely.