case report - Granulosa cell tumor of the ovary after long-term use of tamoxifen and toremifene - Journal of Obstetrics and Gynaecology Research

Granulosa cell tumor of the ovary after long-term use of tamoxifen and toremifene - Tanaka - 2012 - Journal of Obstetrics and Gynaecology Research

Abstract

The relation between the use of tamoxifen and gynecologic tumors has been documented. In this case, a 58-year-old postmenopausal woman had been treated with tamoxifen for 5 years followed by toremifene for 1.5 years due to the presence of stage II estrogen receptor-positive breast cancer. The patient was found to have a stage Ic granulosa cell tumor of the ovary despite undergoing annual gynecologic examinations. This report presents a case of granulosa cell tumor of the ovary after the long-term use of tamoxifen and toremifene

JNCI Commentary (open access): CYP2D6 Genotype as a Marker for Benefit of Adjuvant Tamoxifen in Postmenopausal Women: Lessons Learned

Blogger's Note: see extensive references including current papers regarding this issue

 "Since 2003, there has been considerable interest and a good degree of credence given to the role of cytochrome P450 2D6 (CYP2D6) genotyping to predict tamoxifen benefit in adjuvant therapy (1–5). This construct was based on the fact that a variety of CYP2D6 polymorphisms lead to reduced CYP2D6 enzyme activity and hence result in lower plasma concentrations of endoxifen, a clinically active metabolite of tamoxifen.....


"In the end, it is crucial to obtain data from randomized trials for clinical demonstration of associations between biomarkers and disease outcomes. To advance breast cancer therapy, laboratory observations that raise hypotheses must be at the very core of what we do; however, it is only after independent validation that they can begin guide clinical practice."

1. 15.↵
   1. Regan MM,
   2. Leyland-Jones B,
   3. Bouzyk M,
   4. et al

   . CYP2D6 genotype and tamoxifen response in postmenopausal women with estrogen-responsive early breast cancer: the Breast International Group 1-98 Trial. J Natl Cancer Inst. 2012;104(6):441-451.
2. 16.↵
   1. Rae JM,
   2. Drury S,
   3. Hayes DF,
   4. et al

   . CYP2D6 and UGT2B7 genotype and risk of recurrence in tamoxifen-treated breast cancer patients. J Natl Cancer Inst. 2012;104(6):452-460.

10-year analysis of the ATAC trial: wrong conclusion? : The Lancet Oncology

"The 10-year analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial1 continues to show a difference in its primary endpoint of disease-free survival, which favours anastrozole as adjuvant treatment for postmenopausal women with hormone-responsive breast cancer. Ultimately, however, clinical trials have two aims: either to show improvement in survival, or in its quality.
Anastrozole has failed to meet these criteria when compared with tamoxifen."

Undetectable antimüllerian hormone levels and recovery of chemotherapy-induced ovarian failure in women with breast cancer on an oral aromatase inhibitors

Abstract

OBJECTIVE: Knowledge of the menopause status of a woman with breast cancer is important for good clinical practice. Long-lasting amenorrhea is frequent in this population, often for reasons other than definitive menopause. Antiestrogens like tamoxifen or oral aromatase inhibitors (AIs) may reactivate the ovary causing vaginal bleeding, menstruation, pregnancy, and unopposed endometrial stimulation. In contrast to tamoxifen, AIs are not active against breast cancer in the presence of functional ovaries. Antimüllerian hormone (AMH) is a potential marker of residual ovarian function that can predict not only the onset of menopause but also chemotherapy-induced amenorrhea (CIA) and fertility. We assess the value of AMH in women who recovered from CIA on an AI.

full free access: Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial

full free access The Lancet: Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial : The Lancet Oncology

abstract: Managing menopausal symptoms and depression in tamoxifen users: Implications of drug and medicinal interactions

OBJECTIVE: Tamoxifen, a medication used in the treatment of breast cancer, often induces menopausal symptoms. Certain medications and natural supplements taken or prescribed to alleviate tamoxifen-induced hot flashes and depressive states in women with breast cancer interact with tamoxifen. This paper reviews potentially problematic interactions and offers treatment recommendations.
CONCLUSIONS: Clinicians should remain cautious about using strong inhibitors and/or inducers of cytochrome 2D6 and 3A4 concomitantly with tamoxifen. Use of natural menopausal supplements and diets rich in isoflavones should not be encouraged in tamoxifen users until more data is available. There are however safe treatments for hot flashes and depression in tamoxifen users.

Randomized phase III trial of tamoxifen versus thalidomide in women with biochemical-recurrent-only epithelial ovarian, fallopian tube or primary peritoneal carcinoma after a complete response to first-line platinum/taxane chemotherapy with an evaluation of serum vascular endothelial growth factor

ConclusionThalidomide was not more effective than tamoxifen in delaying recurrence or death but was more toxic. VEGF was not prognostic in this cohort.

EvidenceUpdates: Review: American society of clinical oncology clinical practice guideline: update on adjuvant endocrine therapy for women with hormone recep

CONCLUSION The Update Committee recommends that postmenopausal women with hormone receptor-positive breast cancer consider incorporating AI therapy at some point during adjuvant treatment, either as up-front therapy or as sequential treatment after tamoxifen. The optimal timing and duration of endocrine treatment remain unresolved. The Update Committee supports careful consideration of adverse effect profiles and patient preferences in deciding whether and when to incorporate AI therapy.

BioMed Central Blog : Does genetic test allow prediction of patients’ response to tamoxifen?

Testing for CHEK2 in the cancer genetics clinic: ready for prime time?

Abstract

Narod SA.
Testing for CHEK2 in the cancer genetics clinic: ready for prime time?

The 1100delC mutation of the CHEK2 gene was found to be a cause of breast cancer in 2002. The lifetime risk of breast cancer among women with a mutation and with a family history of breast cancer is approximately 25%. These women are good candidates for screening with MRI and for chemoprevention with tamoxifen. It is reasonable to test for this single mutation when women undergo testing for BRCA1 and BRCA2.

Abstract/free full text - Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer

"Conclusions

We have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted."

Paradigm Change Suggested for Ovarian Cancer

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"Women with biochemically recurrent ovarian cancer who take tamoxifen can gain an additional month of progression-free survival and have fewer side effects than women taking thalidomide, according to a study presented at the recent Society for Gynecologic Oncology’s annual meeting (abstract 2)"
“This is a very well-tolerated, very inexpensive drug, and now we have a randomized controlled, Phase III trial conducted by a cooperative group showing that it actually improves the time to subsequent disease progression,” said Maurie Markman, MD, vice president for clinical research at the University of Texas M.D. Anderson Cancer Center in Houston, who was not involved with the study...."cont'd

Best Evidence Interview: Use of Some SSRIs With Tamoxifen Increases Mortality in Breast Cancer Patients: A Best Evidence Interview With Catherine Kelly, MD

Note: included in interview is discussion of U.S./Canadian/Global research on this subject matter (reminder: Medscape articles are freely accessible with registration)

Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial

Tamoxifen for relapse of ovarian cancer. Cochrane Collaboration review (abstract)

AUTHORS' CONCLUSIONS: We are unable to make any evidence-based recommendations as we found no comparative studies assessing the effectiveness of tamoxifen in women with recurrent ovarian cancer. There is limited evidence on anti-tumour activity from phase 2 studies, but these contain no data on the effect of tamoxifen on symptom control, QOL or the prolongation of life.

Plain language summary

No evidence to suggest tamoxifen benefits patients with relapsed ovarian cancer
Ovarian cancer often spreads before symptoms show. Cytotoxic drugs are often only partly effective and cause severe side-effects. The main aims of treatment for relapsed disease are symptom control and prolongation of life. No data from RCTs or non-RCTs were found, so there was no evidence that tamoxifen was effective and safe as a treatment for relapsed ovarian cancer. Laboratory studies suggest tamoxifen may be effective as a treatment for women with ovarian cancer. Although, uncontrolled non-comparative trials on patients with relapsed ovarian cancer showed tamoxifen may shrink or stabilise tumours in a small number, there is a strong need for an RCT or good quality non-randomised comparative studies to determine the effectiveness and safety of tamoxifen in terms of overall survival, tumour response, symptom control, quality of life and adverse events.

YouTube - Insidermedicine In Depth - February 8, 2010 - combination Paxil/Tamoxifen + clinical commentary

news item: Paxil Blocks Tamoxifen Lowers Survival Odds Against Breast Cancer - Breast Cancer

"Patients taking Paxil and tamoxifen should talk with their doctors about changing their antidepressant, Juurlink said. But he advised against abruptly discontinuing Paxil.
"There is a very real danger to stopping Paxil suddenly. There is a well-described withdrawal syndrome and the risk of depression becoming more severe," he said.
In addition, any transition to another antidepressant should be done gradually over several weeks, he said."