Axillary nodal metastases from carcinoma of unknown primary (CUPAx): a systematic review of published evidence

Abstract

Axillary lymph node metastases from adenocarcinoma or poorly differentiated carcinoma of unknown primary (CUPAx) represent a rare clinical entity without consensus on its biology, management and outcome. We systematically reviewed published CUPAx series and identified 24 retrospective studies enrolling 689 patients from 1975 till 2006. CUPAx affected women at a mean age of 52 years, 66% of whom post-menopausal harbouring low-volume (N1, 48%) or high-volume (52%) nodal disease from ductal adenocarcinoma (83%). Among a total of 446 patients managed with mastectomy, a small breast primary was identified histologically in 321 (72% of cases). Hormone receptor protein expression was observed in 40-50% of cases, while HER2 overexpression in 31%. CUPAx patients were managed with axillary lymph node dissection coupled to mastectomy (59%), primary breast irradiation (26%) or observation (15%). Observation was associated with high locoregional relapse rates (42%) and risk of metastatic spread. Mastectomy or radiotherapy provided locoregional disease control in 75-85% of cases, while adjuvant systemic therapy was associated with a nonsignificant trend for improved survival in few series. Five-year survival ranged from 59.4 to 88% at a median follow-up of 62 months (mean 5-year survival 72%), with axillary tumour burden being the pivotal prognostic factor. CUPAx is associated with similar presentation, biology and outcome to resected node-positive overt breast cancer and should be treated accordingly.

The migration ability of stem cells can explain the existence of cancer of unknown primary site. Rethinking metastasis.

“…Breast tumors commonly metastasize to this site, and this type of CUP is found almost exclusively in women. However, breast tumors were not identified in 28% of 446 women who were diagnosed with this type of CUP and underwent mastectomy and subsequent histological analysis [2,39]. The terms primary tumor and secondary tumor should also be avoided in the absence of a primary tumor.…”

Occult Breast Cancers Manifesting as Axillary Lymph Node Metastasis in Men: A Two-Case Report

“…It has been suggested that occult breast cancer with axillary metastasis should be treated in the same way as breast cancer with a comparable nodal stage is treated [6]. According to a report that analyzed 24 studies on axillary nodal metastasis from CUP, 321 of 446 patients (72%) who underwent mastectomy showed pathological signs of occult breast cancer, which suggests that mastectomy is an effective diagnostic and therapeutic modality [14]. On the contrary, other studies reported that there was no difference in the survival rates of patients, who underwent mastectomy and patients, who preserved their breasts, which suggests that mastectomy is not necessary.…”

Immunohistochemically defined subtypes and outcome in occult breast carcinoma with axillary presentation

“…In fact, previous studies focusing on OBC also evaluated patients with histopathological identification of invasive carcinoma on the breast. A review focusing on 689 patients included in 24 retrospective series of OBC was recently reported [20]. Amongst a total of 446 patients managed with mastectomy, an occult breast primary tumour was eventually identified histologically in 321 patients (72%).…”