Nodal staging affects adjuvant treatment choices in elderly patients with clinically node-negative, estrogen receptor-positive breast cancer.

Background: In response to Choosing Wisely recommendations that sentinel lymph node biopsy (slnb) should not be routinely performed in elderly patients with node-negative (cN0), estrogen receptor-positive (er+) breast cancer, we sought to evaluate how nodal staging affects adjuvant treatment in this population. Methods: From a prospective database, we identified patients 70 or more years of age with cN0 breast cancer treated with surgery for er+ her2-negative invasive disease during 2012-2016. We determined rates of, and factors associated with, nodal positivity (pN+), and compared the use of adjuvant radiation (rt) and systemic therapy by nodal status. Results: Of 364 patients who met the inclusion criteria, 331 (91%) underwent slnb, with 75 (23%) being pN+. Axillary node dissection was performed in 11 patients (3%). On multivariate analysis, tumour size was the only factor associated with pN+ (p = 0.007). Nodal positivity rates were 0%, 13%, 23%, 33%, and 27% for lesions preoperatively sized at 0-0.5 cm, 0.5-1 cm, 1.1-2.0 cm, 2.1-5.0 cm, and more than 5.0 cm. Compared with patients assessed as node-negative, those who were pN+ were more likely to receive axillary rt (lumpectomy: 53% vs. 1%, p < 0.001; mastectomy: 43% vs. 2%, p < 0.001), and adjuvant systemic therapy (endocrine: 82% vs. 69%; chemotherapy plus endocrine: 7% vs. 2%, p = 0.002). Conclusions: Of elderly patients with cN0 er+ breast cancer, 23% were pN+ on slnb. Size was the primary predictor of nodal status, and yet significant rates of nodal positivity were observed even in tumours preoperatively sized at 1 cm or less. The use of rt and systemic adjuvant therapies differed by nodal status, although the long-term oncologic implications require further investigation. Multidisciplinary input on a case-by-case basis should be considered before omission of slnb.

Coordination of radiologic and clinical care reduces the wait time to breast cancer diagnosis.

BACKGROUND: In 2009, a Rapid Access Breast Clinic (rabc) was opened at our urban hospital. Compared with the traditional system (ts), the navigated care through the clinic was associated with a significantly shorter time to surgical consultation. Since 2009, many radiology facilities have introduced facilitated-care pathways for patients with breast pathology. Our objective was to determine if that change in diagnostic imaging pathways had eliminated the advantage in time to care previously shown for the rabc. METHODS: All patients seen in the rabc and the office-based ts in November-December 2012 were included in the analysis. A retrospective chart review tabulated demographic, surgeon, pathology, and radiologic data, including time intervals to care for all patients. The results were compared with data from 2009. RESULTS: In 2012, time from presentation to surgical consultation was less for the rabc group than for the ts group (36 days vs. 73 days, p < 0.001) for both malignant (31 days vs. 55 days, p = 0.008) and benign diagnoses (43 days vs. 79 days, p < 0.001). Comparing the 2012 results with results from 2009, a decline in mean wait time was observed for the ts group (86 days vs. 73 days, p = 0.02). Compared with patients having investigations in the ts, rabc patients with cancer were more likely to undergo surgery within 60 days of presentation (33% vs. 15%, p = 0.04). CONCLUSIONS: The coordination of radiology and clinical care reduces wait times for diagnosis and surgery in breast cancer. To achieve recommended targets, we recommend implementation of more systematic coordination of care for a breast cancer diagnosis and of navigation to surgeons for patients needing surgical care.

Correlation of CD44 expression with proliferative activity of normal human breast epithelial cells in culture.

A number of studies have shown that certain variant isoforms of CD44 are overexpressed in human breast cancer, suggesting their use as indicators of the presence of malignant cells. We now show that CD44 isoform mRNA and protein expression is upregulated in normal human breast epithelial cells (HBEC) when these cells are stimulated to proliferate in culture. Reverse transcription-PCR analysis of cultured normal HBEC revealed complex patterns of CD44 mRNA expression that were indistinguishable from patterns previously shown to be characteristic of tissue samples containing malignant HBEC. CD44v6-expressing cells were identified in cultures generated from FACS-purified populations of either normal luminal (CALLA-MUC-1+) or myoepithelial (CALLA+MUC-1-) cells, even though immunohistochemical analysis of normal breast tissue sections confirmed CD44v6 expression to be limited to the myoepithelium in vivo. Increased expression of both CD44v mRNA and protein in cultured populations of normal HBEC was shown to correlate positively with the proportion of cells that were proliferating (Ki-67+) independent of cell density. These results indicate that activation of CD44 variant isoform expression in HBEC occurs as a normal response to factors that stimulate their proliferation and suggests caution in the use of this marker to identify malignant cells.

Phenotypic and functional characterization in vitro of a multipotent epithelial cell present in the normal adult human breast.

The developmental relationships between the different mammary epithelial cell lineages in the human mammary gland are not well defined. To characterize human breast epithelial cells (HBEC) with progenitor activity, we used flow cytometry and single cell sorting to analyze the distribution of cellular phenotypes in primary cultures of reduction mammoplasties and their associated ability to generate colonies in 2-dimensional (D) and 3-D (collagen gel) culture systems. This approach allowed two distinct types of HBEC progenitor populations to be distinguished on the basis of their differential expression of the MUC-1 glycoprotein, CALLA/CD10 and epithelial-specific antigen (ESA). The first type of progenitor, which is enriched in the MUC-1+/CAL-LA-/ESA+ subpopulation, generated colonies of tightly arranged cells in 2-D cultures and small alveolar-like colonies with a central lumen when cultured in a collagen matrix. The cells produced in the colonies and derived from these MUC-1+/CALLA-/ESA+ progenitors were found to express typical luminal epitopes (keratin 8/18, keratin 19, MUC-1, ESA) and showed low levels of expression of myoepithelial epitopes (keratin 14 and CD44v6). The second type of progenitor, which is present in the MUC-1-to +/-/CALLA +/- to +/ESA+ subpopulation, generated mixed colonies of both luminal and myoepithelial cells when seeded in 2-D and 3-D cultures. In 2-D cultures, the centrally located cells exhibited a luminal morphology and expressed ESA, but were heterogeneous in their expression of MUC-1. Radiating from the periphery of these ESA+ HBEC were highly refractile ESA- teardrop-shaped myoepithelial-like cells. When cultured in a collagen matrix, these bipotent progenitors generated large branched colonies composed of a heterogeneous population of cells, with some of the progeny cells expressing luminal epitopes (keratin 8/18, keratin 19 and MUC-1) and others expressing myoepithelial epitopes (keratin 14 and CD44v6). A third type of progenitor, which became apparent is passaged HBEC cultures and was enriched in the MUC-1-/CALLA+/ESA- subpopulation, was found to generate colonies of cells with an exclusively myoepithelial phenotype. These results provide definitive evidence for the existence of multilineage HBEC progenitors in normal adult human mammary tissue. The phenotypic profile of these cells suggest that these multilineage progenitors are a relatively undifferentiated cell since they express low levels of MUC-1 and that they have a luminal location within the mammary epithelium since they are ESA+. Furthermore, we suggest that the MUC-1+/CALLA-/ESA+ and the MUC-1- to +/-/CALLA +/- to +/ESA+ progenitors we have identified and characterized are candidate in vivo alveolar and ductal progenitors, respectively.

Comparison of partial and modified radical mastectomy in the community setting--"10 years later".

Conservative surgery followed by postoperative radiation is considered equivalent to a modified radical mastectomy (MRM) for the treatment of early breast cancer. It cannot be assumed that results from selected academic centres are equivalent to those obtained in the general community setting, because there may be differences in patient selection or surgical or radiotherapy techniques that may adversely affect outcome. A quality-control study of women who were seen at the British Columbia Cancer Agency and were treated by partial mastectomy (PM) was begun in 1983. Eighty-four women who underwent conservative surgery between January 1979 and November 1982 and were referred to the British Columbia Cancer Agency were matched with 84 women who underwent MRM. The mean follow-up was 10.5 years. At 10 years disease-free survival in both groups was 63%. Survival overall for the PM group was 72.6% and for the MRM group was 69%. The survival rate decreased with increasing size of the tumour and increasing number of nodes. In women with lymph-node involvement there was a survival advantage for those treated by PM and radiation compared with those treated by MRM. The woman's age at diagnosis did not affect these findings. Recurrence and complication rates were similar in both groups, and treatment was considered equivalent.

Multiple giant fibroadenomas in an adolescent female breast.

Fibroadenomas are the commonest breast masses requiring surgery in the adolescent female, but multiple and giant tumours are rare. This case report describes the history and management of a teenager who had multiple giant fibroadenomas in one breast, eventually requiring mastectomy and reconstruction. The literature is reviewed. Tumours in this age group are almost always benign, even the giant and phyllodes tumours. Malignant tumours are extremely rare. Management should involve excision with skin reduction if necessary. The breast should be preserved if at all possible.