Breast cancer is one of the most common cancers in women worldwide and its incidence has been increasing rapidly. Mucinous breast carcinoma (MBC) is a relatively rare type of tumor accounting for only 1%–6% of all breast cancers [123]. MBCs are associated with a good prognosis and have a better prognosis than that for invasive ductal carcinoma (IDC). They usually occur in women aged above 60 years and in postmenopausal women. MBCs consist of small clusters of tumor cells with large amounts of extracellular and extra-luminal mucus in direct contact with the stroma [345]. However, the presence of the mucinous carcinoma pattern in a breast mass is not a guarantee of good prognosis. Attentive gross examination and generous histologic sampling are necessary to ensure that the histologic pattern is pure and, thus, of prognostic significance [4]. MBCs are mostly positive for estrogen and/or progesterone receptors (ER/PR-positive) and negative for human epidermal growth factor receptor 2 (HER-2). Additionally, MBCs are less likely to involve the axillary lymph nodes (ALN) than other types of breast cancer. As such, although they are a form of invasive breast cancer, MBCs tend to be less aggressive and respond well to adjuvant treatment and ultimately have a good prognosis [678]. Different guidelines have been established for adjuvant systemic therapy of MBCs [49]. The National Comprehensive Cancer Network (NCCN) guideline recommends treatment according to the hormone receptor status; patients who are hormone receptor-negative are recommended the same treatment as in other breast cancers with poor prognosis, while those who are hormone receptor-positive are recommended to consider chemotherapy only if they have node positivity. Early-stage MBC patients, such as those with N0 or N1mi stage, should receive endocrine therapy, while patients with node positivity (one or more metastases > 2 mm) could be administered adjuvant chemotherapy [10]. However, most treatment guidelines for adjuvant chemotherapy of MBC were derived from IDC treatment experiences. MBC is a relatively rare type of breast cancer; thus, most MBC studies included few patients and limited follow-up periods. Therefore, the treatment guidelines for MBC have not been rigorously validated [11]. Previous studies have shown that many MBC patients receive adjuvant chemotherapy [61213]. However, adjuvant chemotherapy results in increased side effects, including toxicity, and whether adjuvant chemotherapy benefits survival from MBC remains unclear [14]. Therefore, given the good prognosis of MBC, adjuvant chemotherapy may be overtreatment. Using the Korean Breast Cancer Registry (KBCR), this study aimed to verify whether adjuvant chemotherapy has any clinical benefits in ER-positive MBC and whether adjuvant chemotherapy can be omitted in these patients.

This study investigated the need for chemotherapy in the treatment of ER-positive MBC. Our findings showed that adjuvant chemotherapy did not significantly improve BCSS and OS in most MBC patients. We also found a good prognosis of MBC, similar to previous reports [69]. Among patients with ER-positive MBC, ALN metastasis was a significant prognostic factor for BCSS, while old age, pathologic tumor, and ALN metastasis were significant prognostic factors for OS.

MBC is a relatively rare histologic type of tumor that accounts for only 1%–6% of all breast cancers. MBC is characterized by a large amount of extracellular mucin [16]. Previous studies have shown that MBC has characteristics different from those of other invasive breast cancers, including high ER/PR expression, less ALN metastasis, and lower HER-2 expression [91718], which were also observed in our study. Due to these characteristics, MBC has a better prognosis than those of other invasive breast cancers. MBC can be divided into pure MBC (pMBC) and mixed MBC (mMBC) depending on the quantification of cellularity [19]. pMBC consists exclusively of tumor tissues with mucinous components above 90% while mMBC contains mucinous areas covering more than 50% but less than 90% of the total area, as well as admixing, usually with an infiltrating ductal epithelial component [20]. Recent studies have evaluated the differences in clinicopathological features and survival between pMBC and mMBC [132122]. Nodal positivity in pMBC ranges from 2%–14% [12123], compared to 46%–64% in mMBC [2721]. However, the KBCR does not provide data to distinguish between the histologic subtypes of MBC. Most patients in our study were thought to have pMBC because 16.5% had axillary nodal positivity.

The NCCN guidelines consider hormone receptors to play an important role in the treatment of MBC. Hormone receptor-positive patients are recommended to consider chemotherapy if they have ALN metastasis, whereas adjuvant chemotherapy is not recommended for patients without metastatic ALN. Meanwhile, because ER-negative MBC has a poor prognosis, the recommended treatment strategy is similar to that for other breast cancers [10]. Our results revealed that ER-negativity had a significant effect on BCSS. Due to the low prevalence, limited follow-up period, and good prognosis, few studies on MBC have been conducted, and most of the previous studies had a small sample size. The clinicopathologic factors affecting the prognosis of MBC are unclear. Furthermore, most treatment guidelines for adjuvant chemotherapy of MBC were derived from IDC treatment experiences [14] and have not been rigorously validated [11]. Therefore, the treatment guidelines should be validated to establish more appropriate guidelines for MBC.

Some studies have identified ALN metastasis as the strongest predictor of disease-specific survival because most patients presenting with LN metastases develop distant metastasis [1322]. In our study, ALN metastasis was also the most significant prognostic factor for BCSS and OS. Old age (> 50 years) and pathologic tumor stage were significant factors for OS. Previous studies revealed local or distant recurrence in some MBC patients. As such, many clinicians administer adjuvant chemotherapy similar to those for other breast tumors despite the good prognosis of MBC [61112]. This trend was consistent with our findings. In our study, 1,415 (47.4%) patients received adjuvant chemotherapy; of them, 1,181 patients were ER-positive. However, in contrast to the guidelines, 826 of 1,945 MBC (42.5%) patients with positive ER expression but without ALN metastasis received adjuvant chemotherapy. Current guidelines recommend adjuvant chemotherapy in MBC patients with ER positivity and ALN metastasis [10]. In our study, 348 of 384 (90.6%) patients were administered chemotherapy. These results show that, contrary to guideline recommendations, a large number of patients with MBC undergo chemotherapy in the real world.

Recent studies have reported that luminal breast cancer patients do not equally benefit from adjuvant chemotherapy [242526]. Furthermore, clinical trials have shown that adjuvant chemotherapy may not be necessary even in cases with ALN metastasis or large tumor size in luminal breast cancer [27]. Gene expression profiles have been developed to identify the individual risk of recurrence to avoid unnecessary adjuvant cytotoxic chemotherapy [28]. Chemotherapy is also less effective in MBC because of the higher ER and PR and lower HER-2 expression. These observations suggest that adjuvant chemotherapy can be omitted in MBC, which generally has a good prognosis. However, gene expression profiles cannot be used to predict recurrence risk in MBC due to the abundant mucinous content [11]. Therefore, we investigated the benefit of adjuvant chemotherapy in ER-positive MBC. Several clinical studies have already shown a good prognosis in MBC patients, even those with high-risk factors [71322].

When stratified by pathologic tumor stage, pathologic nodal stage, and age, our Kaplan–Meier curve analysis revealed that, except for N3 stage, adjuvant chemotherapy did not significantly improve BCSS and OS. We did not obtain significant results in pathologic T stage analysis for BCSS and OS due to the sample sizes of T3 and T4 patients. In our study, 94.5% of patients with ER-positive MBC had T1 and T2 stage disease. Pathologic N stage analysis showed differences in BCSS and OS between the chemotherapy and no chemotherapy groups for N2 and N3-stage disease. Only N3 stage showed a significant difference. However, the sample size was too small to interpret these results. N2 and N3-stage disease is also extremely rare among ER-positive MBC patients, accounting for only 3.3% of cases. Further studies are warranted to determine the efficacy of chemotherapy in a larger number of patients with other stages of disease. Our study found that most ER-positive MBC patients had T1 or T2 or N1-stage disease and that chemotherapy did not improve survival in most of these patients. The results of our multivariate analysis also indicated that the omission of adjuvant chemotherapy did not have a significant effect on BCCS and OS, despite the presence of ALN metastasis. Analysis of BCSS and OS for N1 stage showed a lower OS than BCSS in the no chemotherapy group, but the difference was not statistically significant. These results suggest that the patients who did not receive chemotherapy had a higher rate of other-cause deaths because of underlying disease or old age.

Our study had several limitations. First, the KBCR does not record the type of MBC as pure or mixed and provides no detailed information about recurrence. Second, because of the retrospective and voluntary nature of the KBCR, a large portion of data were missing, particularly regarding pathologic details and treatment. These missing data may have affected our results. Furthermore, it is difficult to reach a definitive conclusion due to the retrospective study design. Despite these limitations, our study is valuable in that, to the best of our knowledge, it is the first to investigate the efficacy of adjuvant chemotherapy in ER-positive MBC patients. Our study was also among the few large-scale MBC studies with a relatively long-term follow-up. Further, the KBCR is a nationwide database that prospectively collects data from more than 65% of patients undergoing breast cancer surgery in Korea; thus, our findings may be representative of all women with breast cancer in Korea.

In conclusion, the results of this large retrospective analysis revealed that adjuvant chemotherapy does not improve the prognosis in most ER-positive MBC patients, regardless of ALN metastasis. The good prognosis of patients with MBC was also confirmed. Furthermore, the pathologic nodal stage was the most important factor influencing patient prognosis. Ultimately, adjuvant chemotherapy can be omitted in the treatment of most ER-positive MBC.