Biological response to hormonal manipulation in oestrogen receptor positive ductal carcinoma in situ of the breast

Abstract

Adjuvant antioestrogen therapy with tamoxifen is recommended for all women following breast-conserving surgery for ductal carcinoma in situ (DCIS) to reduce local recurrence, despite 50% of lesions being oestrogen receptor (OR) negative. We have investigated the response to hormone manipulation in DCIS by studying changes in epithelial proliferation and progesterone receptor (PR) expression as surrogate molecular markers of treatment effects in DCIS of known OR status. Women were identified who had undergone diagnostic core biopsy followed by surgery for DCIS 14 -41 days later. Ki67 (a measure of epithelial cell proliferation) and PR expression were determined by immunohistochemistry on paired paraffin sections of the core biopsy and operative specimens for each patient, with OR and HER-2 measured on the operative specimen. Women were divided into three groups according to whether they had changed hormone therapy (stopped hormone replacement therapy (HRT), group 1), continued taking HRT (group 2) or were not taking HRT (group 3) between core biopsy and surgery. In OR-positive (but not in OR-negative) DCIS after oestrogen withdrawal (group 1), a fall in the mean cell proliferation (Po0.01) was observed. A fall in PR expression between core biopsy and surgery was also seen in this group (P ¼ 0.02). No change in either mean cell proliferation or PR expression was seen in the other two groups in OR-positive or -negative DCIS. The fall in proliferation and PR expression occurred regardless of HER-2 status. In conclusion, a biological response to hormone manipulation is only seen in OR-positive DCIS tumours. Any clinical value of antioestrogen therapy is likely to be restricted to this group.

Patterns of Chromosomal Alterations in Breast Ductal Carcinoma In situ

“…Gain of 17q has been associated with amplification of ERBB2, located at 17q12 (38). Studies have shown that the erbB2/her2/neu protein product is overexpressed in 60 -70% of DCIS by immunohistochemistry (39,40), although in only 20 -30% of invasive breast cancers. The higher prevalence of 17q gain in DCIS versus invasive ductal cancer is somewhat counterintuitive given the precursor-product relationship between them.…”

COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ

“…Ki67 and ER scores were calculated as the percentage of positively stained nuclei. Oestrogen receptor positivity was defined as X5% stained nuclei, and has been used in previous studies in DCIS in our unit (Holland et al, 1997;Gandhi et al, 1998Gandhi et al, , 2000Boland et al, 2003b). For each section, a minimum of 1000 cells were scored across randomly selected areas of DCIS at a magnification of  400 using a grid graticule and cell counter.…”

Cyclooxygenase-2 Inhibition Does Not Improve the Reduction in Ductal Carcinoma In situ Proliferation with Aromatase Inhibitor Therapy: Results of the ERISAC Randomized Placebo-Controlled Trial

“…However, conservation surgery is associated with local recurrence rates of between 7% and 30% after 10 years of follow-up compared with <1% following mastectomy (3). Approximately half of all recurrences are invasive cancers (1,2).…”

“…Most patients with DCIS are treated with breast conservation surgery with subsequent adjuvant therapy with radiation and/or tamoxifen (1,2). However, conservation surgery is associated with local recurrence rates of between 7% and 30% after 10 years of follow-up compared with <1% following mastectomy (3).…”

“…Ductal carcinoma in situ (DCIS) accounts for 25% of all the screen-detected breast cancer (1,2). Most patients with DCIS are treated with breast conservation surgery with subsequent adjuvant therapy with radiation and/or tamoxifen (1,2).…”