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Purpose: The prognostic value of estrogen receptor (ER)/progesterone receptor (PgR) expression in ductal carcinoma in situ (DCIS) is unclear. We observed multi-clonality when evaluating ER/PgR expression in the UK/ANZ DCIS trial, therefore, we investigated the prognostic role of both uni-clonal and multi-clonal ER/PgR expression in DCIS. Experimental Design: Formalin-fixed paraffin embedded tissues were collected from UK/ANZ DCIS trial participants (n = 755), and ER/PgR expression was evaluated by IHC in 181 cases (with recurrence) matched to 362 controls by treatment arm and age. Assays were scored by the Allred method and by a newly devised clonal method—analyses categorizing multi-clonal DCIS as ER/PgR-positive as per current practice (Standard) and as ER/PgR-negative (clonal) were performed. Results: ER expression was multi-clonal in 11% (39/356) of ER-positive (70.6%, 356/504) patients. Ipsilateral breast event (IBE) risk was similarly higher in ER-multi-clonal and ER-negative DCIS as compared with DCIS with uni-clonal ER expression. ER-negative DCIS (clonal) had a higher risk of in situ IBE [OR 4.99; 95% confidence interval (CI), 2.66–9.36; P < 0.0001], but the risk of invasive IBE was not significantly higher (OR 1.72; 95% CI, 0.84–3.53; P = 0.14), Pheterogeneity = 0.03. ER was an independent predictor in multivariate analyses (OR 2.66; 95% CI, 1.53–4.61). PgR status did not add to the prognostic information provided by ER. Conclusions: ER expression is a strong predictor of ipsilateral recurrence risk in DCIS. ER-positive DCIS with distinct ER-negative clones has a recurrence risk similar to ER-negative DCIS. ER should be routinely assessed in DCIS, and ER scoring should take clonality of expression into account.

OBJECTIVE To determine the effect of topical ophthalmic administration of 0.005% latanoprost solution on aqueous humor flow rate (AHFR) and intraocular pressure (IOP) in ophthalmologically normal dogs. ANIMALS 12 adult Beagles. PROCEDURES In a masked crossover design involving two 10-day experimental periods separated by a 7-day washout period, dogs were randomly assigned to first receive latanoprost or artificial tears (control) solution and then the opposite treatment in the later experimental period. Each experimental period was divided into a baseline phase (days 1 to 3), baseline fluorophotometry assessment (day 4), treatment phase (1 drop of latanoprost or artificial tears solution administered twice daily in each eye on days 5 to 9 and once on day 10), and posttreatment fluorophotometry assessment (day 10). Measured fluorescein concentrations were used to calculate baseline and posttreatment AHFRs. The IOP was measured 5 times/d in each eye during baseline and treatment (days 5 to 9) phases. RESULTS Mean baseline and posttreatment AHFR values did not differ significantly in either experimental period (latanoprost or control). In the latanoprost period, mean IOP was significantly lower during treatment than at baseline; there was no difference in corresponding IOP values during the control period. In the latanoprost period, mean IOP was significantly higher on the first day of treatment than on subsequent treatment days. CONCLUSIONS AND CLINICAL RELEVANCE In ophthalmologically normal dogs, topical ophthalmic administration of 0.005% latanoprost solution significantly decreased IOP but did not affect AHFR. Thus, the ocular hypotensive effect of latanoprost did not appear to have been caused by a reduction in aqueous humor production. (Am J Vet Res 2019;80:498–504)