Use of the levonorgestrel-releasing intrauterine system in breast cancer patients

Trinh, Xuan Bich; Tjalma, Wiebren A.A.; Makar, Amin; Buytaert, Guy; Weyler, Joost; Dam, Peter van

doi:10.1016/j.fertnstert.2007.05.033

Cited by 91 publications

(51 citation statements)

References 24 publications

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“…46,47 In addition, when used by premenopausal women after initiation of breast cancer treatment, the LNG-IUD does not appear to increase the risk of breast cancer recurrence. 48 Thus, for premenopausal women who wish to retain fertility but have menstrual disturbances, the LNG-IUD seems to be a reasonable, short-term treatment. In postmenopausal women, the LNG-IUD should be removed.…”

Section: Aub Caused By Anatomic Abnormalitiesmentioning

confidence: 99%

“…For women with AUB, the LNG-IUD appears to be safe to use in conjunction with tamoxifen 48 ; however, for irregular or intermittent bleeding in the setting of amenorrhea, premenopausal status should be confirmed before placement. The LNG-IUD does not protect against complex atypical hyperplasia or EC associated with postmenopausal tamoxifen use, [65][66][67] and it should be removed when a woman reaches menopause.…”

Section: Tamoxifen Use and Aubmentioning

confidence: 99%

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Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Bakkum-Gamez

Laughlin

Jensen

et al. 2011

Mayo Clinic Proceedings

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). © 2011 Mayo Foundation for Medical Education and ResearchB reast cancer is the leading cause of cancer death in women in the United States who are aged 20 to 59 years. 1 In 2010, an estimated 207,090 new cases of breast cancer were identified in the United States. 2 Although breast cancer risk increases with age, approximately 35% of breast cancers occur during the reproductive and perimenopausal years. 3 The 5-year relative survival rate for women of all ages with breast cancer diagnosed between 1999 and 2005 is 89%. 3 Of the premenopausal breast cancers diagnosed, approximately 58% are both estrogen receptor (ER) and progesterone receptor (PR) positive, 6% are ER positive only, 17% are PR positive only, and 20% are both ER and PR negative. 4 The management and treatment of breast cancer in premenopausal women can affect menstruation, reproduction, and gynecologic health. Breast cancer treatment can have a marked affect on fertility in women who have delayed childbearing and have fewer remaining reproductive years. Among premenopausal women with breast cancer, more than 50% wish to retain their fertility. 5 AUB = abnormal uterine bleeding; E2 = estradiol; EA = endometrial ablation; EC = endometrial cancer; ER = estrogen receptor; FDA = Food and Drug Administration; GnRH = gonadotropin-releasing hormone; IUD = intrauterine device; LNG = levonorgestrel; NSAID = nonsteroidal anti-inflammatory drug; PR = progesterone receptor; SHBG = sex hormone-binding globulin gynecologic issues and conditions are prevalent in reproductive-age women. In the general population, more than 30% of reproductive-age women fulfill criteria for the diagnosis of menorrhagia, 6 25% have symptomatic fibroids, 7 and nearly 67% have an underlying uterine disorder with potential to cause abnormal uterine bleeding (AUB). 8 Among premenopausal women with breast cancer, management of menstrual disorders, contraception, vasomotor symptoms, and fertility presents a challenge. Common and effective hormonal options are less well studied in this population because of significant concern about recurrence of breast cancer. Herein,we present the challenges and discuss management options for young women with breast cancer who present with various common gynecologic conditions.Articles for this review were identified by searching the PubMed database with no date limitations. PREMENoPAUSAL SEx STERoIDS AND THEIR PHARMACoLoGyPhysiologically, premenopausal women with regular cycles have cyclic variation in levels of estradiol (E2) (15-350 pg/ mL [to convert to pmol/L, multiply by 3.671]) and progesterone (0.2-27 ng/mL [to convert to nmol/L, multiply by 3.18]). These "free" (unbound) hormones are biologically active and can enter a target cell and activate its receptor.

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Section: Aub Caused By Anatomic Abnormalitiesmentioning

confidence: 99%

Section: Tamoxifen Use and Aubmentioning

confidence: 99%

Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Bakkum-Gamez

Laughlin

Jensen

et al. 2011

Mayo Clinic Proceedings

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“…Though Levonorgestrel-releasing intrauterine system (LNG-IUS) was indicated as a suppressor of endometrium proliferation, there is not enough evidence regarding its efficacy in reducing endometrial hyperplasia and cancer (44). Moreover, the use of LNG-IUS in the setting of hormonal therapy for breast cancer, is questionable due to its possible interaction with the antiestrogenic therapy (45). When considering the safety of PEDF treatment to patients with breast cancer-PEDF was already shown to inhibit the growth of breast cancer cells in vitro, to exhibit antitumor activity in vivo, and to reduce the resistance of tumors to tamoxifen (46).…”

Section: Discussionmentioning

confidence: 99%

Pigment Epithelium–Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia

Goldberg

Bar‐Joseph

Grossman

et al. 2015

Molecular Cancer Therapeutics

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Tamoxifen is a cornerstone component of adjuvant endocrine therapy for patients with hormone-receptor-positive breast cancer. Its significant adverse effects include uterine hyperplasia, polyps, and increased risk of endometrial cancer. However, the underlying molecular mechanism remains unclear. Excessive angiogenesis, a hallmark of tumorigenesis, is a result of disrupted balance between pro-and anti-angiogenic factors. VEGF is a proangiogenic factor shown to be elevated by tamoxifen in the uterus. Pigment epithelium-derived factor (PEDF) is a potent anti-angiogenic factor that suppresses strong pro-angiogenic factors, such as VEGF. Our aim was to investigate whether angiogenic balance plays a role in tamoxifen-induced uterine pathologies, elucidate the molecular impairment in that network, and explore potential intervention to offset the proposed imbalance elicited by tamoxifen. Using in vivo mouse models, we demonstrated that tamoxifen induced a dose-dependent shift in endogenous uterine angiogenic balance favoring VEGF over PEDF. Treatment with recombinant PEDF (rPEDF) abrogated tamoxifen-induced uterine hyperplasia and VEGF elevation, resulting in reduction of blood vessels density. Exploring the molecular mechanism revealed that tamoxifen promoted survival and malignant transformation pathways, whereas rPEDF treatment prevents these changes. Activation of survival pathways was decreased, demonstrated by reduction in AKT phosphorylation concomitant with elevation in JNK phosphorylation. Estrogen receptor-a and c-Myc oncoprotein levels were reduced. Our findings provide novel insight into the molecular mechanisms tamoxifen induces in the uterus, which may become the precursor events of subsequent endometrial hyperplasia and cancer. We demonstrate that rPEDF may serve as a useful intervention to alleviate the risk of tamoxifen-induced endometrial pathologies.

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“…Moreover, Kesim et al (2008) and Trinh et al (2008) found out that LNG-IUS significantly prevent the increased risk of endometrial polyps and hyperplasia associated with the use of tamoxifen in women with breast cancer and this reduce patient discomfort while improving treatment adherence. Qi et al (2008) reported that two infertile patients presented with complex atypical EH became pregnant following conservative treatment with LNG-IUS insertion, and histological morphology of endometrial samples after 6 months' exposure to LNG-IUS showed secretory or atrophic glands with decidualized stroma.…”

Section: Discussionmentioning

confidence: 99%

Levonorgestrel-releasing intrauterine device for management of tamoxifen-induced menorrhagia in breast cancer patients

Elnory¹,

El-Habbaa²,

Rageh³

2014

J. Cancer Res. Exp. Oncol.

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This study aimed to evaluate the therapeutic yield of levonorgestrel-releasing intrauterine device (LNG-IUD) for management of tamoxifen induced menorrhagia in women who had mastectomy for treatment of breast cancer. This study included 34 patients who had breast cancer, underwent mastectomy, were maintained on tamoxifen post-operatively for at least 6 months, and had also newly developed menorrhagia throughout their follow-up period. All the patients underwent clinical examination for determination of duration and heaviness of menstrual blood loss (MBL), transvaginal ultrasonography (TVU) and endometrial biopsy for exclusion of abnormal pathology, estimation of blood iron indices and quality of life (QoL) scoring. Baseline endometrial biopsy detected simple endometrial hyperplasia (EH) in 4 patients and 30 patients had proliferative endometrium. Three patients were excluded and 31 patients completed the follow-up period without the need for shift to hysterectomy. Both mean duration and heaviness of MBL showed significant progressive decrease throughout the observation period as compared to baseline data. At the end of follow-up period, 5 women became amenorrheic, 2 women had moderate MBL and 24 women had mild MBL. Iron indices studies showed significant improvement at the end of follow-up as compared to baseline indices and total QoL scoring recorded at 6 and 12 months after enrollment were significantly higher as compared to baseline scores with significantly higher scores at 12 months. LNG-IUD could be considered as an appropriate therapeutic modality for tamoxifen-induced menorrhagia in patients who had mastectomy for breast cancer with significant reduction of duration and severity of MBL and improved QoL and iron indices.

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Use of the levonorgestrel-releasing intrauterine system in breast cancer patients

Cited by 91 publications

References 24 publications

Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Pigment Epithelium–Derived Factor Alleviates Tamoxifen-Induced Endometrial Hyperplasia

Levonorgestrel-releasing intrauterine device for management of tamoxifen-induced menorrhagia in breast cancer patients

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