Use of the Levonorgestrel-Releasing Intrauterine System and Breast Cancer

Backman, Tiina; Rauramo, Ilkka; Jaakkola, Kimmo; Inki, Pirjo; Vaahtera, Katja; Launonen, Aino; Koskenvuo, Markku

doi:10.1097/01.aog.0000178754.88912.b9

Cited by 137 publications

(60 citation statements)

References 15 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.…”

Section: Aub Caused By Anatomic Abnormalitiesmentioning

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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). © 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%

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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“…On the other hand, no increase in BC risk was found in a population-based case-control study [14]. The role of hormone-releasing intrauterine device (HR IUD) in the etiology of BC has also been under discussion, and the results are somewhat contradicting [15][16][17][18]. With respect to use of hormone replacement therapy (HRT), several studies have indicated that HRT use increases the risk of BC.…”

Section: Introductionmentioning

confidence: 99%

Use of exogenous hormones and the risk of breast cancer: results from self-reported survey data with validity assessment

Heikkinen

Koskenvuo

Malila

et al. 2015

Cancer Causes Control

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Purpose Main aim was to estimate the association between use of exogenous hormones and breast cancer (BC) risk in a large population-based survey, and to assess the representativeness and overall validity of the data. Methods The survey 'Women's Health and Use of Hormones' was conducted in Finland in 2009, including 7,000 BC cases and 20,000 matched population controls. Conditional logistic regression was used to estimate odds ratios and their 95 % confidence interval. For validation, exposure prevalences were compared with population data from Statistics Finland and two large population-based surveys. Results We found positive associations with BC risk and exclusive use of hormone-releasing intrauterine device (HR IUD) in postmenopausal women (1.48, 95 % CI 1.10-1.99), when compared to never-users of any hormonal contraceptive and considering only prediagnostic use in cases. Regarding use of other hormonal contraceptives (HC), a positive association between long HC use (C2 years) and BC was observed in both groups, OR being 1.37 (95 % CI 1.12-1.68) for premenopausal and 1.11 (95 % CI 1.03-1.20) for postmenopausal women, when compared to never-users of other HC. Conclusions Observed association between HR IUD use and risk of BC in postmenopausal women is worrying and deserves further attention. Selection bias seemed not to explain this result. Considering the increasing popularity of HR IUD use in, e.g., USA, impact of possible adverse effects in public health could be significant.

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“…The Backman study included LNG-IUS users of all ages with the dominant group being 35-39 years old. There was no significant difference in BC incidence between LNG-IUS users and the general female population in any of the evaluated age groups; however, in the 35-39 age group (i.e., women reaching late 30's/approximating early 40's), the incidence was higher in LNG-IUS users and the differences trended towards significance (p = 0.056) [9]. In the Soini study (women aged 30-49 years with an average follow-up of [10 years), LNG-IUS users had an increased risk for ductal breast cancer (standardized incidence ratio [SIR] 1.20) and lobular breast cancer (SIR 1.33; latter mostly luminal subtypes) [11].…”

Section: Discussionmentioning

confidence: 74%

“…Of the four studies investigating the association between LNG-IUS use and BC, our study design is more similar to the studies reported by Backman et al and Soini et al [9,11,12]. In these studies involving 17,360 LNG-IUS users (all indications) and 93,843 LNG-IUS users (for treating/preventing menorrhagia), respectively, BC incidence was compared between LNG-IUS users and the general female population.…”

Section: Discussionmentioning

confidence: 92%

“…Data on the incidence of cancer and particularly BC in women of fertile age using LNG-IUS are inconsistent. Two large retrospective studies (involving [17,000 LNG-IUS users, and [25,000 BC cases/controls) demonstrated no increase in BC risk with LNG-IUS, whereas two database studies from Finland involving [93,000 LNG-IUS users demonstrated an increased BC risk [9][10][11][12]. To date, the published studies were all in Finnish/German population, included a variety of ages, and did not control for prior or concurrent and subsequent hormonal interventions.…”

Section: Introductionmentioning

confidence: 99%

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Does levonorgestrel-releasing intrauterine system increase breast cancer risk in peri-menopausal women? An HMO perspective

Siegelmann‐Danieli

Katzir

Landes

et al. 2017

Breast Cancer Res Treat

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Purpose To evaluate the association between levonorgestrel-releasing intrauterine system (LNG-IUS) use and breast cancer (BC) risk. Methods A cohort of all Maccabi Healthcare Services (MHS) female members aged 40-50 years between 1/2003 and 12/2013 was used to identify LNG-IUS users as ''cases,'' and 2 age-matched non-users as ''controls.'' Exclusion criteria included: prior BC diagnosis, prior (5 years pre-study) and subsequent treatment with other female hormones or prophylactic tamoxifen. Invasive tumors were characterized by treatments received (chemotherapy, hormonal therapy, trastuzumab, or combination thereof). Results The analysis included 13,354 LNG-IUS users and 27,324 controls (mean age: 44.1 ± 2.6 vs. 44.9 ± 2.8 years; p \ 0.0001). No significant differences in 5-year KaplanMeier (KM) estimates for overall BC risk or ductal carcinoma in situ occurrence were observed between groups. There was a trend towards higher risk for invasive BC in LNG-IUS users (5-year KM-estimate: 1.06% vs. 0.93%; p = 0.051). This difference stemmed primarily from the younger women (40-45 years; 0.88% vs. 0.69%, p = 0.014), whereas in older women (46-50 years), it was non-significant (1.44% vs. 1.21%; p = 0.26). Characterization of invasive BC by treatment demonstrated that LNG-IUS users had similar proportions of tumors treated with hormonal therapy, less tumors treated with trastuzumab, (7.5% vs. 14.5%) and more tumors treated with chemotherapy alone (25.8% vs. 14.9%; p = 0.041). Conclusions In peri-menopausal women, LNG-IUS was not associated with an increased total risk of BC, although in the subgroup of women in their early 40's, it was associated with a slightly increased risk for invasive tumors.

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Use of the Levonorgestrel-Releasing Intrauterine System and Breast Cancer

Abstract: The results suggest that the use of the levonorgestrel-releasing intrauterine system is not associated with an increased risk of breast cancer.

Cited by 137 publications

References 15 publications

Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Challenges in the Gynecologic Care of Premenopausal Women With Breast Cancer

Use of exogenous hormones and the risk of breast cancer: results from self-reported survey data with validity assessment

Does levonorgestrel-releasing intrauterine system increase breast cancer risk in peri-menopausal women? An HMO perspective

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