Non-Invasive Breast Carcinoma Treatment Outcomes
Overview
Non-invasive breast carcinoma, distinct from invasive forms, can lead to local recurrence post-surgery, potentially progressing to invasive carcinoma and distant metastasis, impacting breast cancer prognosis. This study, involving 93 cases among 872 primary breast cancers, assessed outcomes. Surgical interventions, radiation, and endocrine therapy were common treatments. Local recurrence occurred in 3 patients (0.3%), but distant metastasis was absent. Overall survival stood at 98.0%, and breast cancer-specific survival reached 100.0%. While non-invasive breast carcinoma mirrors invasive forms in local recurrence, it generally holds a favorable prognosis without distant metastasis. The role of isolated tumor cells in sentinel lymph nodes in non-invasive carcinoma warrants further investigation.
Introduction
Breast cancer is categorized as invasive or non-invasive, depending on whether tumor cells breach the ductal basement membrane. Invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) are common forms, while lobular carcinoma is less frequent. Transition from DCIS to invasive carcinoma and distant metastasis can occur due to genetic and epigenetic changes within a single cell. In IDC, genetic abnormalities, clonal expansion, and basement membrane penetration lead to distant metastasis.
Non-invasive carcinomas like DCIS and lobular carcinoma in situ (LCIS) are typically localized, posing no distant metastatic threat unless they progress to invasive carcinoma after surgical treatment.
Sentinel lymph nodes (SLNs) in the axilla serve as the first line of defense against tumor metastasis, assessed through methods like one-step nucleic acid amplification (OSNA). OSNA, frozen sections, and definitive histology show similar outcomes for stages I and II breast cancer. Sentinel lymph node biopsy (SLNB) is standard, especially for DCIS with potential invasive features.
The presence of tumor cells in SLNs might result from diagnostic procedures or microvascular invasion, but their clinical significance and the pathway of non-invasive carcinoma’s systemic extension remain unclear. This retrospective cohort study aims to explore breast cancer recurrence and survival in non-invasive carcinoma patients, shedding light on whether it behaves as a local or systemic disease.
Method
Inclusion Criteria
This retrospective study focused on women diagnosed with non-invasive carcinoma (International Union for Cancer Control TNM stage 0) between May 2008 and March 2022 at the Hiroshima Mark Clinic. To be included in the study patients had to have a final pathological diagnosis of non-invasive carcinoma based on surgical specimens.
Exclusion Criteria
Patients meeting any of the following criteria were excluded from the study:
- Presence of microinvasive or concurrent invasive cancer.
- Receipt of neoadjuvant therapy.
- Initial diagnosis of non-invasive carcinoma based on preoperative vacuum-assisted biopsy that was later determined to be invasive carcinoma upon surgical specimen analysis.
The study received ethical approval from the Ethics Committee of Hiroshima Mark Clinic (no. HMC-04), and all patients provided informed consent for their respective treatments.
Results
Among 872 patients diagnosed with primary breast cancer at the clinic, 94 (10.7%) were identified as having non-invasive carcinoma. One patient who did not undergo surgical treatment was excluded from the study, leaving a cohort of 93 patients for analysis. This cohort consisted of 87 cases of ductal carcinoma in situ (DCIS), two cases of lobular carcinoma in situ (LCIS), three cases with co-existing DCIS and LCIS, and one case of non-invasive apocrine carcinoma. The median age of these patients was 47 years, ranging from 27 to 80 years.
Sixty-three patients underwent outpatient surgery at the clinic, while 30 patients had inpatient surgery at an affiliated hospital. Among these patients, 79 (84.9%) had hormone receptor (HR)-positive tumors, and 20 (21.5%) had human epidermal growth factor receptor 2 (HER-2)-positive tumors. Tumor nuclear grades were distributed as 22 (23.6%) in grade 1, 46 (49.4%) in grade 2, and 23 (24.7%) in grade 3.
Various types of preoperative diagnostic biopsies were performed, with fine-needle aspiration cytology (FNA) being the most common (n = 78). The predominant surgical procedure was partial mastectomy (Bp/Bq) with sentinel lymph node biopsy (SLNB), performed in 59 cases (63.4%), followed by Bp/Bq and total mastectomy (Bt) with SLNB, each performed in 15 cases (16.1%). Among the 26 patients who underwent SLNB with OSNA analysis, 24 (92.3%) showed elevated negativity with isolated tumor cells.
Endocrine therapy (ET) was administered to 64 (68.8%) patients, while postoperative radiation therapy (RT) was given to 73 (78.4%) patients, with 43 of them receiving RT boosters.
Over a median follow-up period of 1891 days (ranging from 5 to 4004 days), three patients experienced breast cancer recurrence. One patient had local recurrence from DCIS to invasive ductal carcinoma (IDC) and underwent total mastectomy (Bt) with SLNB. Another patient experienced local recurrence from non-invasive to invasive lobular carcinoma (ILC) and underwent repeat partial mastectomy. The third patient had local DCIS recurrence and opted for an alternative treatment approach.
No breast cancer-related deaths occurred during the study period, but one patient passed away due to a stroke. The cumulative overall survival (OS) rate for the entire cohort was 98.0%, and the breast cancer-specific survival (BCSS) rate was 100%.
Discussion
In this cohort of 93 patients with non-invasive breast carcinoma, the study observed no instances of distant metastasis following surgical therapy. However, local recurrence was noted in three cases, two of which were successfully managed through total mastectomy and repeat partial mastectomy, while the third patient opted for alternative treatment. Notably, the two surgically-treated cases that experienced local recurrence developed invasive carcinoma, but this transition to invasiveness did not lead to distant metastasis, challenging the notion that local recurrence is a direct cause of increased breast cancer mortality.
These findings align with previous research indicating that postoperative radiation therapy (RT), potentially in combination with adjuvant endocrine therapy (ET) using tamoxifen (TAM), can reduce local recurrence rates in ductal carcinoma in situ (DCIS). However, the presence of isolated tumor cells in sentinel lymph nodes (SLNs) raises questions about the possibility of metastasis without the full invasive conversion of non-invasive carcinoma. While no distant metastasis was observed in this study, the role of these isolated cells in the development of distant metastasis remains uncertain.
Patients with DCIS have a low incidence of distant metastasis, but the reduction of local recurrence does not necessarily correlate with improved breast cancer mortality. This suggests that tumor cells in DCIS may access the breast duct microvasculature, potentially leading to systemic disease. In this study, OSNA revealed isolated tumor cells in SLNs in the majority of cases, with some patients having undergone preoperative vacuum-assisted biopsy (VAB). The mechanical disruption of the tubular component during core needle biopsy (CNB) has been proposed as a potential cause of micrometastasis in DCIS. Moreover, while repeat histopathological evaluation of surgical specimens has identified occult invasion in some DCIS cases, it does not account for all cases.
The study also highlighted that the incidence of isolated tumor cells in SLNs did not differ significantly between patients who did and did not undergo VAB. Additionally, a proportion of circulating tumor cells have been found in the peripheral blood and bone marrow of patients with DCIS, suggesting that these cells may enter the bloodstream before crossing the epithelial basement membrane.
Given these findings, sentinel lymph node biopsy (SLNB) is no longer recommended for patients diagnosed with DCIS by CNB and treated with breast-conserving surgery (BCS). SLNB can be safely performed even after the final pathological diagnosis of invasive breast carcinoma, as SLN metastasis is rare in pure DCIS cases. This approach eliminates the risk of complications and reduces medical costs while maintaining diagnostic accuracy.
Distant metastasis in DCIS cases is a rare occurrence and may reflect microvascular invasion into the breast ducts, even when comprehensive histological sectioning of surgical specimens does not reveal invasive lesions. The study suggests that isolated tumor cells in SLNs and distant metastases may coexist at the time of initial diagnosis, possibly developing through breast cancer stem cell activity during disease progression.
Overall, the study raises questions about whether additional systemic therapies beyond endocrine therapy are required to prevent distant metastasis and improve breast cancer mortality in different subgroups of DCIS patients. While postoperative radiation therapy may reduce local recurrence, it may not significantly impact breast cancer mortality. Further research is needed to better understand the mechanisms underlying the transition to distant metastases in DCIS and to explore potential therapeutic interventions. However, the study acknowledges its limitations, primarily its retrospective nature and the relatively small sample size, resulting in infrequent local recurrence and no observed distant metastasis within the cohort.
Conclusion
The study findings indicate that postoperative radiation therapy (RT) and endocrine therapy (ET) are effective in reducing the occurrence of local recurrence in cases of non-invasive carcinoma. Importantly, instances of local recurrence transitioning from non-invasive to invasive carcinoma do not lead to an increase in the rate of distant metastasis. Such local recurrences can be successfully managed with additional surgical interventions and do not have a detrimental impact on breast cancer mortality.
However, the clinical significance of the presence of isolated tumor cells in the sentinel lymph nodes (SLNs) concerning their potential to contribute to distant metastasis as a systemic disease remains unclear. More extensive research on isolated tumor cells in SLNs from patients with non-invasive breast carcinoma is needed to gain a deeper understanding of the mechanisms underlying tumor progression in these cases.
In summary, the study underscores the importance of postoperative RT and ET in preventing local recurrence in non-invasive carcinoma cases and suggests that transitioning from non-invasive to invasive carcinoma does not necessarily lead to distant metastasis. It highlights the need for further investigations into the role of isolated tumor cells in SLNs to enhance our comprehension of disease progression in these patients.
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