Invasive papillary carcinoma is a rare type of invasive ductal carcinoma, classified as WHO-O code 8503/3 and defined as showing a predominantly papillary morphology (>90 %) in the invasive component. Because of its histological similarity, papillary metastases from other primary sites like lung or ovary carcinoma should be considered in the differential diagnosis [1]. In this case, there was no evidence of metastases from carcinoma at any other primary sites, and primary breast cancer was diagnosed.
In terms of clinical characteristics, Liu et al. [3] reported that invasive papillary carcinoma occurs mostly in the postmenopausal period and is associated with better 5-year overall survival rate and disease-free survival rate than general invasive ductal carcinoma, although the distribution of the four biological subtypes (luminal A, luminal B, HER2, triple-negative) was similar to that of general-type invasive ductal carcinoma.
Generally, when we find papillary lesion in a core needle biopsy specimen, it is sometimes difficult to determine whether the lesion is benign or malignant and to identify the existence of an invasive lesion. Therefore excisional biopsy is recommended for many cases [4]. In the present case, we were able to gather a sufficient volume of specimen by vacuum-assisted large core needle biopsy, making the diagnosis of invasive papillary carcinoma easy. However, we could not reconfirm this diagnosis at surgery, as pCR had been achieved. To the best of our knowledge, this represents the first report of the therapeutic effect of neoadjuvant endocrine therapy for invasive papillary carcinoma.
According to the National Comprehensive Cancer Network (NCCN) guidelines [5], neoadjuvant endocrine therapy for breast cancer may be considered for receptor-positive disease in postmenopausal patients with clinical stage IIA to IIIA, but definitive guidelines are lacking in terms of duration or medication. Clinical practice guidelines published by the Japanese Breast Cancer Society also state that neoadjuvant endocrine therapy may be considered for receptor-positive, HER2-negative disease in postmenopausal patients, but mostly for patients who are unable to undergo or do not consent to surgery [6]. Compared with neoadjuvant chemotherapy, the pCR rate is usually low with neoadjuvant endocrine therapy, but a higher probability of achieving breast-conserving surgery and a lower risk of severe complications may be provided [7]. However, there is no clear relationship between antitumor effects and long-term survival, and further discussion about indications for neoadjuvant endocrine therapy and predictive factors is needed.
The pCR rate is one of the prognostic factors that we can assess outcome in patients undergoing neoadjuvant chemotherapy [8]. However, pCR can be achieved in only a minority of patients with ER-positive disease, irrespective of the chemotherapeutic agents used. Recent consensus papers on neoadjuvant endocrine therapy in breast cancer have indicated that pCR rates ranges from 1 to 8 % in patients with tumors expressing ER [9]. When it comes to neoadjuvant endocrine therapy, the relationship between pCR and overall survival is unclear. Aiming for pCR with neoadjuvant endocrine therapy is thus difficult, and clinicians must try to identify the optimal window for attempting curative surgery while monitoring the therapeutic effect. In terms of the optimal duration for neoadjuvant endocrine therapy, a panel discussion at St. Gallen in 2013 [10] reported that most of the experts believed neoadjuvant endocrine treatment should be continued until maximal response, rather than performing surgery after following a predefined protocol for neoadjuvant chemotherapy. Paepke et al. [11] compared effects between letrozole treatment for 4 and 8 months, finding a significant increase in response rate (57 vs. 90 %, respectively), and noted that longer treatments may allow for an increase in tumor reduction rates. Allevi et al. [12] reported that pCR rate increased up to 17.5 % with 12 months of neoadjuvant letrozole treatment, compared to 5.0 % with 8 months and 2.5 % with 4 months. Prolonged neoadjuvant letrozole treatment is well tolerated with a favorable toxicity profile and results in further tumor volume reduction, and thus may provide incremental benefits to patients for conservative surgery and the induction of a higher rate of pCR. In our case, we considered that pCR was achieved due to the high level of tumor ER expression, and by the long neoadjuvant treatment up to 12 months.