scholarly journals Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia

2019 ◽  
Vol 37 (19) ◽  
pp. 1629-1637 ◽  
Author(s):  
Andrea DeCensi ◽  
Matteo Puntoni ◽  
Aliana Guerrieri-Gonzaga ◽  
Silvia Caviglia ◽  
Franca Avino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Intraepithelial Neoplasia ◽  
Hazard Ratio ◽  
Number Needed To Treat ◽  
Ductal Hyperplasia ◽  
Patient Reported

PURPOSE Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen ( P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

scholarly journals High Prevalence of Premalignant Lesions in Prophylactically Removed Breasts From Women at Hereditary Risk for Breast Cancer

2003 ◽  
Vol 21 (1) ◽  
pp. 41-45 ◽  
Author(s):  
N. Hoogerbrugge ◽  
P. Bult ◽  
L.M. de Widt-Levert ◽  
L.V. Beex ◽  
L.A. Kiemeney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Ductal Carcinoma In Situ ◽  
Odds Ratio ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Prophylactic Mastectomy ◽  
Premalignant Lesions ◽  
Ductal Hyperplasia

Purpose: Women with a hereditary predisposition for breast cancer have an extremely high risk of developing invasive breast carcinoma, and many women consider prophylactic mastectomy to avoid this risk. The use of prophylactic mastectomy is still debated. Identification of frequent premalignant lesions in mastectomy specimens would support the preventive concept of prophylactic mastectomy. Patients and Methods: We performed a prospective study of breast specimens from 67 women at extremely high genetic risk of breast cancer, with or without previous breast cancer, who were undergoing prophylactic mastectomy (66% were carriers of a BRCA1 or BRCA2 mutation). Breast specimens were studied by radiographic and macroscopic examination of 5-mm tissue slices, with subsequent histology of suspicious lesions and random samples from each quadrant of the breast and the nipple area. Results: In 57% of the women, one or more different types of high-risk histopathologic lesions were present: 37% atypical lobular hyperplasia, 39% atypical ductal hyperplasia, 25% lobular carcinoma-in-situ, and 15% ductal carcinoma-in-situ. A 4-mm invasive ductal carcinoma was found in one woman with ductal carcinoma-in-situ. None of these lesions was detected at palpation or mammography, which were performed before the mastectomy. The presence of high-risk lesions was independently related to age older than 40 years (odds ratio, 6.6; P = .01) and to bilateral oophorectomy before prophylactic mastectomy (odds ratio, 0.2; P = 0.02). Conclusion: Many women at high risk of hereditary breast cancer develop high-risk histopathologic lesions, especially after the age of 40 years. Surveillance does not detect such high-risk histopathologic lesions.

scholarly journals Ductal Carcinoma In Situ Progression in Dog Model of Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 418 ◽  
Author(s):  
Sulma Mohammed ◽  
Sagar Utturkar ◽  
Maxwell Lee ◽  
Howard Yang ◽  
Zhibin Cui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Invasive Carcinoma ◽  
Ductal Carcinoma ◽  
Canine Model ◽  
Invasive Cancer ◽  
Ductal Hyperplasia

The mechanisms that drive ductal carcinoma in situ (DCIS) progression to invasive cancer are not clear. Studying DCIS progression in humans is challenging and not ethical, thus necessitating the characterization of an animal model that faithfully resembles human disease. We have characterized a canine model of spontaneous mammary DCIS and invasive cancer that shares histologic, molecular, and diagnostic imaging characteristics with DCIS and invasive cancer in women. The purpose of the study was to identify markers and altered signaling pathways that lead to invasive cancer and shed light on early molecular events in breast cancer progression and development. Transcriptomic studies along the continuum of cancer progression in the mammary gland from healthy, through atypical ductal hyperplasia (ADH), DCIS, and invasive carcinoma were performed using the canine model. Gene expression profiles of preinvasive DCIS lesions closely resemble those of invasive carcinoma. However, certain genes, such as SFRP2, FZD2, STK31, and LALBA, were over-expressed in DCIS compared to invasive cancer. The over-representation of myoepithelial markers, epithelial-mesenchymal transition (EMT), canonical Wnt signaling components, and other pathways induced by Wnt family members distinguishes DCIS from invasive. The information gained may help in stratifying DCIS as well as identify actionable targets for primary and tertiary prevention or targeted therapy.

scholarly journals The Emerging Roles of Steroid Hormone Receptors in Ductal Carcinoma in Situ (DCIS) of the Breast

2018 ◽  
Vol 23 (4) ◽  
pp. 237-248 ◽  
Author(s):  
Hugo Villanueva ◽  
Sandra Grimm ◽  
Sagar Dhamne ◽  
Kimal Rajapakshe ◽  
Adriana Visbal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Hormone Receptors ◽  
Ductal Carcinoma ◽  
Clinical Problem ◽  
Experimental Models ◽  
Steroid Hormone Receptors ◽  
Cancer Risk Factors

Abstract Ductal carcinoma in situ (DCIS) is a non-obligate precursor to most types of invasive breast cancer (IBC). Although it is estimated only one third of untreated patients with DCIS will progress to IBC, standard of care for treatment is surgery and radiation. This therapeutic approach combined with a lack of reliable biomarker panels to predict DCIS progression is a major clinical problem. DCIS shares the same molecular subtypes as IBC including estrogen receptor (ER) and progesterone receptor (PR) positive luminal subtypes, which encompass the majority (60–70%) of DCIS. Compared to the established roles of ER and PR in luminal IBC, much less is known about the roles and mechanism of action of estrogen (E2) and progesterone (P4) and their cognate receptors in the development and progression of DCIS. This is an underexplored area of research due in part to a paucity of suitable experimental models of ER+/PR + DCIS. This review summarizes information from clinical and observational studies on steroid hormones as breast cancer risk factors and ER and PR as biomarkers in DCIS. Lastly, we discuss emerging experimental models of ER+/PR+ DCIS.

scholarly journals Different Biological Action of Oleic Acid in ALDHhigh and ALDHlow Subpopulations Separated from Ductal Carcinoma In Situ of Breast Cancer

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0160835
Author(s):  
Hoe Suk Kim ◽  
Minji Jung ◽  
Sul Ki Choi ◽  
Woo Kyung Moon ◽  
Seung Ja Kim
Keyword(s):  
Breast Cancer ◽  
Oleic Acid ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Biological Action

Advocating Nonsurgical Management of Patients With Small, Incidental Radial Scars at the Time of Needle Core Biopsy: A Study of 77 Cases

2015 ◽  
Vol 139 (9) ◽  
pp. 1137-1142 ◽  
Author(s):  
Cathleen Matrai ◽  
Timothy M. D'Alfonso ◽  
Lindsay Pharmer ◽  
Michele B. Drotman ◽  
Rache M. Simmons ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Core Biopsy ◽  
Carcinoma In Situ ◽  
Invasive Carcinoma ◽  
Ductal Carcinoma ◽  
Lobular Carcinoma ◽  
Radial Scar ◽  
Needle Core Biopsy ◽  
Ductal Hyperplasia

Context Radial scars are benign sclerosing lesions that are routinely excised when diagnosed in a needle core biopsy. Optimal management for patients with incidental and small (≤5 mm) radial scars is uncertain. Objective To assess pathologic upgrade of radial scars diagnosed in needle core biopsy samples and identify a subset of patients who could benefit from conservative management. Design Patients with a diagnosis of radial scar in a needle core biopsy who underwent excision of the biopsied area were identified. Radial scars greater than 5 mm in size and those with coexisting atypia, carcinoma, and papillary lesions were excluded. After histologic-radiographic correlation, rates of pathologic upgrade were assessed. Results Seventy-seven radial scars diagnosed in 66 patients were included. Overall, 9 of 77 (12%) showed upgrade to a high-risk lesion (6 lobular carcinoma in situ, 2 atypical ductal hyperplasia, 1 atypical lobular hyperplasia), while none (0%) showed upgrade to invasive carcinoma or ductal carcinoma in situ. One of 22 incidental radial scars (4.5%) showed upgrade on excision versus 6 of 36 (16.7%) for radial scars considered to be the radiographic target (P = .23). Older age was associated with upgrade (P < .001). Conclusions No incidental or small (≤5 mm) radial scars excised revealed invasive carcinoma or ductal carcinoma in situ on excision. Provided there is good pathologic-radiologic concordance, it appears reasonable for these patients to be managed conservatively.

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