Multidisciplinary Treatment for Locally Advanced Mucinous Breast Cancer

Breast cancer is broadly classified into four subtypes when stratified by estrogen receptor and human epidermal growth factor receptor type 2 (HER2): luminal, luminal-HER2, triple negative, and HER2 subtypes. The luminal breast cancer is the most indolent and common type and is often treated with hormone therapy.

Locally advanced breast cancers (LABCs) are defined as inoperable large breast cancers without distant metastasis [1]. Basic therapeutic strategy of them is similar to that of breast cancers with distant metastasis. Hormonal therapy, therefore, is the mainstay in the treatment of luminal LABCs.

Vast majority of mucinous breast cancers are classified as luminal subtypes and generally show slow growing character [2]. Consequently, breast oncologists have an extremely rare chance to treat mucinous LABC and, even if present, generally treat such case not with chemotherapy but with some kind of endocrine therapy to maintain quality of life of the patients [3].

LABCs often present unpleasant symptoms such as bleeding and massive exudate with dirty pus, markedly deteriorating quality of life of the patients. Therefore, even if first-line hormone therapy is not effective, multidisciplinary treatment aiming for local control can be a feasible therapeutic strategy due to indolent biology of mucinous LABC.

We herein report a case of mucinous LABC successfully treated with multidisciplinary treatment including preoperative chemotherapy and surgery using lattisimus dorsi musculocutaneous (LDMC) flap [4] at least from an aspect of local control. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000539717).

A 50-year-old premenopausal woman had noticed a right breast tumor for more than 5 years and was referred to our hospital for the treatment of breast tumor-induced unpleasant symptoms. Inspection showed a huge and exposed breast tumor on her right chest wall (Fig. 1a). Computed tomography (CT) showed an oval solid tumor (Fig. 2a), lymph node swelling both in the axilla and parasternum (Fig. 2b, c), and no distant metastases. Positron emission tomography/CT showed maximum standardized uptake values of 7.3 and 3.1 in the main tumor and in the regional lymph nodes, respectively. Core needle biopsy of the tumor showed atypical cells growing in a papillary fashion in the abundant mucus, leading to the diagnosis of mucinous carcinoma. Immunostaining showed that the tumor had positive estrogen receptor of 96.8%, positive progesterone receptor of 11.6%, negative HER2 (Hercep test score 0), and low Ki-67 labelling index of 11%. Under the judgment of luminal mucinous LABC, the patient initially received tamoxifen plus leuproreline therapy, unfortunately failing to regress the huge tumor. To get favorable local control, the patient thereafter received sequential chemotherapy, i.e., anthracycline-containing chemotherapy followed by bevacizumab plus paclitaxel therapy, resulting in marked tumor shrinkage (Fig. 1b, 2d). Axillar and parasternal lymph nodes, however, remained unchanged in size (Fig. 2e, f). Due to the strong patient’s preference for long-lasting local control after the tumor regression with the sequential chemotherapy, the patient further underwent mastectomy and regional lymph node dissection including removal of the still enlarged parasternal lymph nodes followed by covering of the large skin defect with a LDMC flap using a spindle skin island, 15 × 8 cm in size (Fig. 1c). Postoperative pathological study showed sparse cancer cell remnants with abundant mucus in both the primary tumor and the dissected lymph nodes (Fig. 3a–f). The patient refused to receive post mastectomy radiotherapy and has been well without any recurrences on fulvestrant and palbociclib therapy for 21 months.

Response rates of neoadjuvant chemotherapy differ markedly among breast cancer subtypes; pathological complete response (pCR) rate ranges from around 10% for luminal type breast cancer to over 50% for HER2 type breast cancer [5]. Breast cancer patients generally show favorable survival after achieving pCR with the neoadjuvant chemotherapy but hardly show pCR with any kinds of neoadjuvant endocrine therapy.

It is well known that breast cancers with favorable biology show poorer response to chemotherapy than those with aggressive phenotypes. Hortobagyi’s algorithm [3], therefore, recommends that patients with non-life-threatening metastatic luminal breast cancer should be initially treated with endocrine therapy not to be deteriorated of their quality of life. Breast oncologists, however, rarely have a chance to treat mucinous LABC due to the indolent biology of mucinous breast cancer. This patient had a slight mental disorder and had left the breast tumor untreated for many years, resulting in an extremely rare case of mucinous LABC.

Patient’s strong preference for good and long-lasting local control made us resect the huge breast cancer using the LDMC flap after the marked shrinkage of it with the sequential chemotherapy. Clinical impact of parasternal node removal on survival has already been negated for decades [6]. The idea to get, at least clinically, complete tumor resection made us remove the still enlarged parasternal lymph nodes in addition to mastectomy and axillary dissection. Two enlarged parasternal lymph nodes were easily removed through the large surgical field after both tumor resection and a short segment resection of one costal cartilage, causing no intra- and postoperative major complications. Pathological results, i.e., sparse but viable cancer remnants, clearly showed the advantage of parasternal lymph node removal for better local control.

Pathological examination revealed sparse viable cancer cells left in the parasternal lymph nodes. Breast oncologists, therefore, need careful attention to the evaluation of antitumor efficacy against breast mucinous carcinoma [7]. In short, the presence of abundant mucus easily leads to an underestimate of the tumor shrinkage effect even when observed of its marked cancer cell death after some kind of anti-cancer therapy. On the other hand, minute cancer cell clusters can reside in the mucus even when no image evaluation modalities including positron emission tomography/CT can depict the viable cancer cell remnants.

In the treatment of metastatic breast cancer, it is well known that the addition of bevacizumab to chemotherapy increases side effects without improving overall survival but improves the overall response rate [8, 9]. We, therefore, added bevacizumab to preoperative chemotherapy for favorable tumor shrinkage followed by better local control.

No tumor regression with the preoperative tamoxifen therapy does not directly imply the inefficacy of tamoxifen therapy against this breast cancer. It, however, is true that tamoxifen did not at least have a strong antitumor effect on this breast cancer. We, therefore, have postoperatively treated the patient with fulvestrant and palbociclib.

At least now, it is difficult for us to assess the long-term efficacy of this treatment against the present mucinous LABC. It, however, is noteworthy that this treatment has made the patient no longer have to worry about how to deal with bleeding or dirty exudate from the LABC on carrying out the daily life. Consequently, judging not from the perspective of cure but from that of improving quality of life of the patient, surgical therapeutic intervention in this case can be judged as extremely excellent.

Breast oncologists should note that multidisciplinary treatment including both preoperative chemotherapy and skin defect covering using LDMC flap is a feasible therapeutic option with the intent of favorable local control even for mucinous LABCs.

This article does not contain any studies involving human participants or animals performed by any of the authors. Ethical approval was not required for this case study in accordance with local or national guidelines. Written informed consent was obtained from the patient for the publication of this case report and accompanying images.

The authors have no conflicts of interest to declare.

The authors have no funding sources to declare.

M.H. designed the study concept. S.O. drafted the manuscript. H.N. treated the patient with chemotherapy.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.