Can tamoxifen cause a significant mammographic density change in breast parenchyma?

Konez, Orhan; Goyal, Manish; Reaven, Robert E.

doi:10.1016/s0899-7071(01)00329-1

Cited by 21 publications

(22 citation statements)

References 15 publications

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“…One possibility is that raloxifene reduced mammographic density to a greater degree than did tamoxifen resulting in differential "unmasking" of in situ cancers among the women taking raloxifene as compared with those taking tamoxifen. Published literature speaks against this possibility, however, showing little effect on mammographic density by raloxifene (13,14) and variable effects with tamoxifen (15,16).…”

Section: Discussionmentioning

confidence: 99%

Carcinoma In Situ Outcomes in National Surgical Adjuvant Breast and Bowel Project Breast Cancer Chemoprevention Trials

Vogel

Costantino²,

Wickerham³

et al. 2010

JNCI Monographs

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Selective estrogen receptor modulators (SERMs) are established in the treatment of estrogen receptor (ER)-positive breast cancer, and four decades of basic and preclinical research have shown them to be ideal agents for the reduction of the risk of breast cancer in highrisk pre-and postmenopausal women. The National Surgical Adjuvant Breast and Bowel Project (NSABP) has conducted many clinical trials that used SERMs for the treatment and prevention of breast cancer. The trials were designed to assess a number of clinical and pathological outcomes including both invasive and in situ breast carcinomas. Here, we summarize the previously published data from two of those trials and also highlight the most recent data related to in situ events in the Study of Tamoxifen and Raloxifene (STAR) NSABP breast cancer risk reduction trial using tamoxifen.In 1992, The National Cancer Institute and the NSABP launched the Breast Cancer Prevention Trial (BCPT, P-l) (1,2). The primary aim of this trial was to determine whether tamoxifen prevented invasive breast cancer in women at increased risk. Women eligible for the trial were 60 years or older, were 35-59 years of age with a 5-year predicted risk of breast cancer of at least 1.66%, or had a history of lobular carcinoma in situ (LCIS). Risk was estimated using the model developed by Gail et al. (3,4). During 5 years of recruitment, 13 388 women entered the trial and were randomly assigned to receive tamoxifen (20 mg daily) or placebo therapy.The trial was stopped when statistical significance was achieved in a number of study endpoints after a median follow-up time of 54.6 months. Among the 13 175 women with evaluable endpoints, 368 invasive and noninvasive breast cancers occurred. There was a 49% reduction in overall risk of invasive breast cancer with tamoxifen: there were 175 cases of invasive breast cancer in the placebo group compared with 89 in the tamoxifen group (risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.39 to 0.66; P < .0001). The annual event rate for invasive breast cancer among women taking tamoxifen was 3.4 per 1000 women compared with 6.8 per 1000 women taking placebo.For the purposes of this evaluation (and in the original publication), both ductal carcinoma in situ (DCIS) and LCIS-both

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Section: Discussionmentioning

confidence: 99%

Carcinoma In Situ Outcomes in National Surgical Adjuvant Breast and Bowel Project Breast Cancer Chemoprevention Trials

Vogel

Costantino²,

Wickerham³

et al. 2010

JNCI Monographs

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“…Because a reduction in mammographic density appears to be a strong indicator of a woman's response to tamoxifen therapy in a preventive setting, [4][5][6][7][8][9] we tested the hypothesis that density change after adjuvant tamoxifen therapy has an influence on breast cancer-specific survival.…”

confidence: 99%

Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients With Breast Cancer

Humphreys

Eriksson

et al. 2013

JCO

119

133

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Purpose Tamoxifen treatment is associated with a reduction in mammographic density and an improved survival. However, the extent to which change in mammographic density during adjuvant tamoxifen therapy can be used to measure response to treatment is unknown. Patients and Methods Overall, 974 postmenopausal patients with breast cancer who had both a baseline and a follow-up mammogram were eligible for analysis. On the basis of treatment information abstracted from medical records, 474 patients received tamoxifen treatment and 500 did not. Mammographic density was measured by using an automated thresholding method and expressed as absolute dense area. Change in mammographic density was calculated as percentage change from baseline. Survival analysis was performed by using delayed-entry Cox proportional hazards regression models, with death as a result of breast cancer as the end point. Analyses were adjusted for a range of patient and tumor characteristics. Results During a 15-year follow-up, 121 patients (12.4%) died from breast cancer. Women treated with tamoxifen who experienced a relative density reduction of more than 20% between baseline and first follow-up mammogram had a reduced risk of death as a result of breast cancer of 50% (hazard ratio, 0.50; 95% CI, 0.27 to 0.93) compared with women with stable mammographic density. In the no-tamoxifen group, there was no statistically significant association between mammographic density change and survival. The survival advantage was not observed when absolute dense areas at baseline or follow-up were evaluated separately. Conclusion A decrease in mammographic density after breast cancer diagnosis appears to serve as a prognostic marker for improved long-term survival in patients receiving adjuvant tamoxifen, and these data should be externally validated.

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“…While mammographic density does not appear to be associated with endogenous levels of sex hormones [13,16], postmenopausal women taking combined estrogen and progestin hormone replacement therapy have been reported to have increased breast density compared to those who do not [1,[17][18][19]. Tamoxifen, a selective estrogen receptor modulator that is approved as a breast cancer prevention therapy, is associated with reduction in IGF-1 and mammographic density [20][21][22][23][24][25][26]. To date only the IBIS 1 trial has shown an association between breast density reduction and reduction in breast cancer risk among women randomized to tamoxifen [27].…”

Section: Introductionmentioning

confidence: 99%

A randomized, placebo-controlled trial (NCIC CTG MAP.2) examining the effects of exemestane on mammographic breast density, bone density, markers of bone metabolism and serum lipid levels in postmenopausal women

Cigler

Richardson²,

Yaffe

et al. 2011

Breast Cancer Res Treat

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We hypothesized that exemestane (EXE) would reduce mammographic breast density and have unique effects on biomarkers of bone and lipid metabolism. Healthy postmenopausal women were randomized to EXE (25 mg daily) or placebo (PLAC) for 12 months and followed for a total of 24 months. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms and secondary endpoints were changes in serum lipid levels, bone biomarkers, and bone mineral density (BMD). Ninety-eight women were randomized (49 to EXE; 49 to PLAC) and 65 had PD data at baseline and 12 months. Among women treated with EXE, PD was not significantly changed from baseline at 6, 12, or 24 months and was not different from PLAC. EXE was associated with significant percentage increase from baseline in N-telopeptide at 12 months compared with PLAC. No differences in percent change from baseline in BMD (lumbar spine and femoral neck) were observed between EXE and PLAC at either 12 or 24 months. Patients on EXE had a significantly larger percent decrease in total cholesterol than in the PLAC arm at 6 months and in HDL cholesterol at 3, 6, and 12 months. No significant differences in percent change in LDL or triglycerides were noted at any time point between the two treatment arms. EXE administered for 1 year to healthy postmenopausal women did not result in significant changes in mammographic density. A reversible increase in the bone resorption marker N-telopeptide without significant change in bone specific alkaline phosphatase or BMD during the 12 months treatment period and 1 year later was noted. Changes in lipid parameters on this trial were modest and reversible.

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Can tamoxifen cause a significant mammographic density change in breast parenchyma?

Cited by 21 publications

References 15 publications

Carcinoma In Situ Outcomes in National Surgical Adjuvant Breast and Bowel Project Breast Cancer Chemoprevention Trials

Carcinoma In Situ Outcomes in National Surgical Adjuvant Breast and Bowel Project Breast Cancer Chemoprevention Trials

Mammographic Density Reduction Is a Prognostic Marker of Response to Adjuvant Tamoxifen Therapy in Postmenopausal Patients With Breast Cancer

A randomized, placebo-controlled trial (NCIC CTG MAP.2) examining the effects of exemestane on mammographic breast density, bone density, markers of bone metabolism and serum lipid levels in postmenopausal women

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