Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial

Detre, Simone; Ashley, S.; Mohammed, Kabir; Smith, Ian; Powles, Trevor J.; Dowsett, Mitch

doi:10.1158/1940-6207.capr-16-0247-t

Cited by 5 publications

(7 citation statements)

References 22 publications

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“…Mortality information was not included in that report. 10 8.5-year dietary intervention, dietary fat intake was significantly but moderately reduced to 24.3% of energy; intakes of fruits, vegetables, and grains were all significantly increased; and body weight, while not an intervention target, was significantly reduced in the intervention group. 28 Through 19.6 years median follow-up, although breast cancer incidence was lower in the intervention group, the finding was not statistically significant.…”

Section: Whi Dm Trialmentioning

confidence: 87%

Breast Cancer Prevention: Time for Change

Chlebowski

Aragaki

Pan

2021

JCO Oncology Practice

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Agency breast cancer prevention guidelines for other than hereditary cancers have not materially changed in 20 years; endocrine-targeted agents (then, tamoxifen; now, adding raloxifene and aromatase inhibitors) reduce good prognosis estrogen receptor (ER)–positive, progesterone receptor (PR)–positive cancers without reducing deaths from breast cancer. Across three tamoxifen placebo-controlled prevention trials (N = 23,360) begun almost 30 years ago, although there were 226 fewer breast cancer cases, there were nine more deaths from breast cancer in the tamoxifen groups. Following clinical advances, currently more than half of breast cancer cases are solved problems with extremely low risk of death. As endocrine-targeted agents commonly prevent these cancers, widespread implementation of current prevention strategies may not reduce deaths from breast cancer. Compared with other breast cancers, ER-positive, PR-negative cancers and triple-negative cancers have inferior survival (90.6% v 83.8% v 78.1%, respectively; P < .001). Against this background, in the Women's Health Initiative Dietary Modification randomized trial (N = 48,835), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.77; 95% CI, 0.64 to 0.94) and deaths from breast cancer were reduced 21% ( P = .02). In the Women's Health Initiative randomized, placebo-controlled trial evaluating conjugated equine estrogen (N = 10,739), ER-positive, PR-negative cancers were statistically significantly reduced in the intervention group (hazard ratio, 0.44; 95% CI, 0.27 to 0.74) and deaths from breast cancer were reduced 40% ( P = .04). These findings suggest that reexamination of breast cancer risk reduction strategies and clinical practice is needed.

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Section: Whi Dm Trialmentioning

confidence: 87%

Breast Cancer Prevention: Time for Change

Chlebowski

Aragaki

Pan

2021

JCO Oncology Practice

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“…Вклад тирозинкиназы EGFR в механизмы неэффективности гормональной терапии несомненен, на что указывает большое количество проведенных исследований, свидетельствующих о том, что экспрессия мРНК гена EGFR и его продукта значительно выше в опухолевой ткани больных, не отвечающих на гормонотерапию тамоксифеном [51][52][53]. Проведенное нами исследование согласуется с представленными данными и указывает на то, что эстроген-позитивные опухоли, экспрессирующие высокие значения EGFR, потенциально резистентны к тамоксифену [54].…”

Section: компоненты Pi3k / Akt / Mtor как молекулярные маркеры ответа на терапию тамоксифеномunclassified

Pi3k/Akt/Mtor: Contribution to the Tumor Phenotype Sensitive to Tamoxifen

Dronova

Бабышкина

Матвиенко

et al. 2021

Rossijskij bioterapevtičeskij žurnal

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The PI3K/Akt/mTOR is a key signaling system that binds oncogenes and various receptors to many cell functions, promotes estrogen resistance, and is the most frequently activated signaling pathway in malignant neoplasm, including breast cancer (BC). About 70 % of BC is hormone‑receptor positive and the endocrine therapy is the main component of treatment for hormone‑receptor positive BC patients. Tamoxifen remains one of the basic drugs for adjuvant endocrine therapy in estrogen‑positive BC patients. However, due to acquired resistance to this drug, 25–30 % of patients develop a relapse or disease progression. Resistance to tamoxifen is one of the key clinical problems in the treatment of estrogen‑positive BC. The potential mechanisms of tamoxifen resistance may be associated with crosstalk between estrogen receptors and PI3K/Akt/mTOR signaling. This review summarizes the current literature data on the role of the PI3K/Akt/mTOR signaling pathway in the mechanisms of hormonal resistance, including a complete characterization of its main components and the features of PI3K/Akt/mTOR interaction with estrogen receptors. The results of studies of the main components of the cascade as molecular markers of response to tamoxifen therapy in estrogen‑positive BC patients are presented. Further study of the PI3K/Akt/mTOR crosstalk with various signaling pathways will contribute to both the understanding of carcino‑ genesis and the development of new molecular‑targeted anticancer drugs for the treatment of tamoxifen‑ resistant breast tumors.

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“…In this issue of Cancer Prevention Research, Detre and coworkers (2) provide the first of two final reports of the pioneering Royal Marsden Prevention Trial (RMPT). The first report of the RMPT was a vanguard study of 200 patients (3) that grew to recruit a total of 2,471 high risk women randomized to placebo or tamoxifen (20mg daily) for eight years.…”

mentioning

confidence: 99%

“…The first report of the RMPT was a vanguard study of 200 patients (3) that grew to recruit a total of 2,471 high risk women randomized to placebo or tamoxifen (20mg daily) for eight years. The authors (2) note, after a median of 18.4 years of follow-up, a 32% reduction in ER/PR positive primary breast cancers but only after the 8 years of tamoxifen was complete. This is a demonstration of the consistent “carry over protective effect” of long term estrogen deprivation (LTED) therapies used to treat or prevent breast cancer (4).…”

mentioning

confidence: 99%

“…The report by the RMPT (2) states that two publications catalyzed their commitment to consider a chemoprevention trial with the breast cancer treatment medicine tamoxifen (6). The RMPT, under the leadership of Professor Trevor Powles CBE, justified their bold strategy because long-term tamoxifen treatment prevented, almost entirely, ER positive rat mammary carcinogenesis (7).…”

mentioning

confidence: 99%

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The 4Ps of Breast Cancer Chemoprevention: Putting Proven Principles into Practice

Jordan

2017

Cancer Prevention Research

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The pioneering Royal Marsden Tamoxifen Prevention Trial, recruited 2471 eligible high risk women to be randomized to either placebo or tamoxifen (20mgs daily) for eight years. Breast cancer incidence was evaluated at a median of 18.4 years from the study start. There was a 32% reduction in estrogen/progesterone receptor (ER/PR) positive breast cancers after tamoxifen treatment finished. Translational research, to study “the good, the bad, and the ugly of tamoxifen” in the 1980’s subsequently ensured women’s safety from possible increases in osteoperosis, coronary heart disease, and endometrial cancer. Other tamoxifen chemoprevention trials followed. The result of laboratory research was the unanticipated discovery of raloxifene to prevent osteoporosis and breast cancer at the same time. A new group of medicines, now known as Selective ER Modulators (SERMs), was established. Indeed, the ability to prevent or delay multiple diseases with a single cheap medicine has the potential to alleviate pressure on healthcare systems that are overwhelmed. It is a priority to educate physicians appropriately to apply recommended proven medicines as preventives.

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Immunohistochemical Phenotype of Breast Cancer during 25-Year Follow-up of the Royal Marsden Tamoxifen Prevention Trial

Abstract: The randomized, double-blinded Royal Marsden Tamoxifen Breast

Cited by 5 publications

References 22 publications

Breast Cancer Prevention: Time for Change

Breast Cancer Prevention: Time for Change

Pi3k/Akt/Mtor: Contribution to the Tumor Phenotype Sensitive to Tamoxifen

The 4Ps of Breast Cancer Chemoprevention: Putting Proven Principles into Practice

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