Fertility drugs and the risk of breast cancer: a meta-analysis and review

Zreik, Tony G.; Mazloom, Ali; Chen, Yanli; Vannucci, Marina; Pinnix, Chelsea C.; Fulton, Stephanie; Hadziahmetovic, Mersiha; Asmar, Nadia; Munkarah, Adnan; Ayoub, Chakib M.; Shihadeh, Ferial; Berjawi, Ghina; Hannoun, Antoine; Zalloua, Pierre; Wogan, Christine F.; Dabaja, Bouthaina S.

doi:10.1007/s10549-010-1140-4

Cited by 60 publications

(36 citation statements)

References 37 publications

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“…Twelve of these articles also included meta-analysis of observational studies [4, 5, 10, 12, 18-21, 27, 49, 55, 62]. Another 14 articles on meta-analyses of observational studies were also identified [63][64][65][66][67][68][69][70][71][72][73][74][75][76] ( Table 1). The meta-analyses addressed diverse medications including antidiabetics, antihyperlipidemics, antihypertensives, antirheumatics, drugs for osteoporosis, and drugs for other conditions.…”

Section: Discussionmentioning

confidence: 99%

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

et al. 2014

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“…Clomiphene citrate is a non-steroidal, selective ER modulator with both agonistic and antagonistic activity; it is widely used for ovulation induction in women with anovulatory causes of infertility (Klip et al, 2000). Several studies have pointed toward an association between clomiphene citrate exposure and breast cancer risk, and while a recent meta-analysis did not confirm this finding, this result was hampered by the lack of long-term follow-up for the majority of available studies used to power the analysis (Zreik et al, 2010). Clomiphene citrate binds ER at multiple locations in the body.…”

Section: Discussionmentioning

confidence: 99%

Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro

Cooley¹,

Matthews²,

Zelivianski³

et al. 2011

Human Reproduction

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background: Breast cancer development involves a series of mutations in a heterogeneous group of proto-oncogenes/tumor suppressor genes that alter mammary cells to create a microenvironment permissive to tumorigenesis. Exposure to hormones during infertility treatment may have a mutagenic effect on normal mammary epithelial cells, high-risk breast lesions and early-stage breast cancers. Our goal was to understand the association between infertility treatment and normal and cancerous breast cell proliferation. methods: MCF-10A normal mammary cells and the breast cancer cell lines MCF-7 [estrogen receptor (ER)-positive, well differentiated]and HCC 1937 (ER-negative, aggressive, BRCA1 mutation) were treated with the weak ER activator clomiphene citrate and hormones that are increased during infertility treatment. Direct effects of treatment on cell proliferation and colony growth were determined.results: While clomiphene citrate had no effect on MCF-10A cells or MCF-7 breast cancer cells, it decreased proliferation of HCC 1937 versus untreated cells (P ¼ 0.003). Estrogen had no effect on either MCF-10A or HCC 1937 cells but, as expected, increased cell proliferation (20-100 nM; P ≤ 0.002) and colony growth (10-30 nM; P , 0.0001) of MCF-7 cells versus control. Conversely, progesterone decreased both proliferation (P ¼ 0.001) and colony growth (P ¼ 0.01) of MCF-10A cells, inhibited colony size of MCF-7 cells (P ¼ 0.01) and decreased proliferation of HCC 1937 cells (P ¼ 0.008) versus control. hCG (100 mIU/ml) decreased both proliferation (P ≤ 0.01) and colony growth (P ≤ 0.002) of all three cell lines.conclusions: Although these data are preclinical, they support possible indirect estrogenic effects of infertility regimens on ER-positive breast cancer cells and validate the potential protective effect of pregnancy-related exposure to hCG.

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“…Besides, invasive BRCA1 breast tumors are often high grade and rapidly growing [33,34]. While a possible linkage between IVF treatment and breast cancer risk has extensively been studied in the general population [35], safety of IVF with regards to the risk for breast cancer has not been systematically studied in female BRCA1/2 carriers. Gonadotropin use for IVF results in a rise in estrogens.…”

Section: Discussionmentioning

confidence: 99%

Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors

Derks-Smeets

Die-Smulders

Mackens

et al. 2014

Breast Cancer Res Treat

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PurposePreimplantation genetic diagnosis (PGD) is a reproductive option for BRCA1/2 mutation carriers wishing to avoid transmission of the predisposition for hereditary breast and ovarian cancer (HBOC) to their offspring. Embryos obtained by in vitro fertilisation (IVF/ICSI) are tested for the presence of the mutation, only BRCA-negative embryos are transferred into the uterus. The suitability and outcome of PGD for HBOC is evaluated. MethodsObservational cohort study on PGD treatments for HBOC carried out in two of WesternEurope's largest PGD centres from 2006 until 2012. Male carriers, asymptomatic female carriers, and breast cancer survivors were eligible. If available, PGD on embryos cryopreserved before chemotherapy was possible. Generic PGD-PCR tests were developed based on haplotyping, if necessary combined with mutation detection. Results 70couples underwent PGD for BRCA1/2. 42/71 carriers (59.2%) were female, six (14.3%) of whom have had breast cancer prior to PGD. In total, 145 PGD cycles were performed. 720 embryos were tested, identifying 294 (40.8%) as BRCA-negative. Of fresh IVF/PGD cycles, 23.9% resulted in a clinical pregnancy. Three cycles involved PGD on embryos cryopreserved before chemotherapy; two of these women delivered a healthy child. Overall, 38 children were liveborn. Two BRCA1 carriers were diagnosed with breast cancer shortly after PGD treatment, despite negative screening prior to PGD. ConclusionsPGD for HBOC proved to be suitable, yielding good pregnancy rates for asymptomatic carriers as well as breast cancer survivors. Because of two cases of breast cancer shortly after treatment, maternal safety of IVF(/PGD) in female carriers needs further evaluation. [2,3]. The prevalence of germline BRCA1/2 mutations is estimated at 0.1-1.0% in the general population, making HBOC one of the more prevalent autosomal dominant genetic disorders [4,5].Carriers of a BRCA1/2 mutation have a 50% risk of passing this predisposition to their offspring. There are several reproductive options to circumvent this, but only two lead to a child genetically related to both partners: prenatal diagnosis and preimplantation genetic diagnosis (PGD). Prenatal diagnosis on the one hand, involves genetic testing of a fetus for the presence of a familial BRCA1/2 mutation during pregnancy, followed by pregnancy termination in case of an unfavourable result. Although applied on a small scale, reports regarding clinical experience with prenatal diagnosis for HBOC are not available in the literature to date. Preimplantation genetic diagnosis (PGD) on the other hand, involves in vitro fertilisation (IVF) with intracytoplasmic sperm injection (ICSI), followed by genetic testing of the embryos for the presence of a familial BRCA1/2 mutation before intrauterine transfer.PGD has been successfully applied since 1990 for an expanding list of monogenic disorders and chromosomal abnormalities [6]. In 2003, the Ethics Taskforce of the European Society of Human Reproduction and Embryology stated that it is acceptable to ...

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Fertility drugs and the risk of breast cancer: a meta-analysis and review

Cited by 60 publications

References 37 publications

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

Potential increased risk of cancer from commonly used medications: an umbrella review of meta-analyses

Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro

Hereditary breast and ovarian cancer and reproduction: an observational study on the suitability of preimplantation genetic diagnosis for both asymptomatic carriers and breast cancer survivors

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