Hereditary female cancers: Breast, ovarian, and endometrial

Article Outline

• Abstract
• 1. Introduction
• 2. BRCA1/BRCA2
• 3. BRCA3: on the road to identification
  • 3.1. Common low-penetrance breast cancer susceptibility SNPs
• 4. Screening
  • 4.1. Issues and testing
  • 4.2. Risk reduction: ovarian and fallopian tube cancer
  • 4.3. Risk reduction: breast cancer
  • 4.4. Management without documented mutation
• 5. Lynch syndrome
  • 5.1. Diagnosis of lynch syndrome
  • 5.2. Screening
  • 5.3. Prevention
• 6. Unopposed estrogen stimulation and endometrial cancer
  • 6.1. Screening
  • 6.2. Treatment
• 7. Is there a place for IVF, IVF–ET and PGD in prevention of breast cancer
• 8. Conclusion
• References
• Copyright

Abstract 

Hereditary cancers breast, ovarian, and endometrial cancers comprise a significant portion of cancers affecting women. This paper strives to review the genetics and current screening, prophylaxis, and treatment of these malignancies.

KEYWORDS: Cancer, BRCA, Breast, Ovarian, Endometrial

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1. Introduction 

With the continuing advancements in genetic technology, understanding hereditary ovarian and breast cancer is becoming ever more important. The syndrome of hereditary breast and ovarian cancer is actually the inheritance of a susceptibility to cancer not the cancer itself. The syndrome is marked by several family members with breast and/or ovarian cancer. These cancers may appear in any combination and onset at an early age is also a characteristic. Women with this genetic susceptibility have a much higher risk of developing cancer than the general population and, therefore, screening by their clinician is extremely important. By identifying the affected women, appropriate prevention measures can be used to reduce their overall risk.

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2. BRCA1/BRCA2 

Breast and ovarian cancers can be caused by mutations in genes BRCA1 on chromosome 17 and BRCA2 on chromosome 13. Germ line BRCA1 or BRCA2 mutations account for 10% of ovarian cancers, 20–40% of breast cancers that cluster in families and less than 5% of breast cancers, overall (1), (2), (3), (4), (5). There are greater than 1200 identified mutations for BRCA1 and greater than 1300 for BRCA2 and the prevalence of a mutation in one of these genes is estimated to be 1 in 300 to 1 in 800 in the general population (1), (2), (3), (4). However, in several ethnic groups such as Ashkenazi Jews the prevalence is as high as 1 in 40. These mutations that are found more often in certain ethnic groups are termed founder mutations. The groups affected include Ashkenazi Jews, French Canadians, Icelanders, and others. The affected individual inherits a mutation in one allele or a copy of BRCA1 or BRCA2 but they still maintain one normal copy. Over the lifetime the second normal copy may develop a mutation. This can occur via two-hit hypothesis. The inheritance pattern is autosomal dominant with a relatively high penetrance. Therefore, a woman with a BRCA1/BRCA2 mutation could have a lifetime risk of breast cancer as high as 60% and 40% risk of ovarian cancer depending on the mutation. In some studies, the risk of breast cancer has been reported to be as high as 74% (Table 1).

Table 1. Published estimates of cancer risk for BRCA1 and BRCA2 mutation carriers.

Site	Population risk (1)	Risk in BRCA1 and BRCA2 mutation carriers
Breast	∼8% by age 70	Risk of primary breast cancer:
		BRCA1 and BRCA2: 56–87% by age 70
		82% by age 80
		33–50% by age 50
		Risk of contralateral breast cancer:
		BRCA1: 48% risk by age 50, 64% by age 70
		BRCA 2: 37% by age 50, 50% by age 70
		BRCA1: 20% within 5years of first diagnosis
		BRCA2: 12% within 5years of first diagnosis
Ovary	∼1% by age 70	BRCA1: 23–44% by age 70–80
		BRCA1: 54% by age 80
		BRCA2: 27% by age 70
		BRCA2: 23% by age 80
		10-fold increased risk following breast cancer
		16% following breast cancer (BRCA2)
Colona	2% by age 70	BRCA1: ∼2-fold increase in relative risk
		BRCA2: no apparent increase in risk
Prostatea	∼8% by age 70	BRCA1: 7.67% (North America) by age 70
		BRCA2: 3- to 7-fold increase in relative risk 8% by age 70, 20% by age 30
Male breast cancera	<0.05% by age 70	BRCA2: 6% by age 70
Pancreatic cancera	∼0.5% by age 70	BRCA1: 2- to 3-fold increase in relative risk; 1.16% (males). 1.26% (females) by age 70
		BRCA2: 3- to 4-fold increase in relative risk: 1–2% by age 70
Uterusa	1.5% by age 70	BRCA1: 2- to 3-fold increase in relative risk; 2.47% by age 70
Cervixa	0.6% by age 70	BRCA1: 3- to 4-fold increase in relative risk: 2.16% by age 50, 3.57% by age 70

The protein product of BRCA1 is multifunctional and involved in DNA repair, transcription, regulation of cell cycle, and protein ubiquitination. The majority of the mutations here involve shortening of the gene product with resultant loss of function. An estimated 0.2% of the general population carries the BRCA1 mutation while the estimate rises in Ashkenazi Jews to 2%. A woman with this mutation has a lifetime risk of ovarian cancer of 40% and breast cancer 60% (Table 1).

BRCA2 codes for a DNA repair protein. Like BRCA1, a mutation in both alleles will result in the loss of a functional DNA repair protein and development of breast and ovarian cancer. A germline mutation for women in BRCA2 increases the lifetime risk of breast cancer to 60% and to 20% for ovarian cancer (Table 1). Interestingly, men are at an increased risk for breast cancer when they possess a germline BRCA2 mutation.

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3. BRCA3: on the road to identification 

Except for the high breast cancer risk in BRCA1 and BRCA2 mutation carriers as well as the risk for breast cancer in certain rare syndromes caused by mutations in TP53, STK11, PTEN, CDH1, NF1 or NBN, familial clustering of breast cancer remains largely unexplained. Despite significant efforts, BRCA3 could not be identified, but several reports have recently been published on genes involved in DNA repair and SNPs associated with an increased breast cancer risk (6).

3.1. Common low-penetrance breast cancer susceptibility SNPs 

High density single nucleotide polymorphisms are now available as tools for genome wide association studies to determine genetic variance associated with an increased breast cancer risk. Currently, there is a growing list of reports on common SNPs in genes or chromosomal loci that have been identified in genome-wide association studies: FGFR2, LSP1, MAP3K1, TGFB1, TOX3, as well as a locus on 2q35 and 8q (6).

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4. Screening 

Assessment of a patient’s risk for these hereditary cancers is integral to every OBGYN practice due to the relatively high prevalence of carriers for BRCA1 and BRCA2 mutations (1 in 300 to 800 in the general population). Screening begins by questioning the patient about them and their family’s history of breast and ovarian cancer (Table 2). A full genetic risk assessment would be provided by a physician with an expertise in heritable cancers. In addition to information gathering and risk estimation, the full assessment involves counseling and genetic testing if applicable. Criteria have been developed in order to determine whether a patient should proceed with a full risk assessment. There are two sets of criteria that stratify patients into risk groups. The first set identifies patients with 20–25% chance of having inherited germline mutation putting them at increased risk for breast and ovarian cancer. The second set identifies patients with more than a 5–10% chance of the same mutations. The first group is strongly recommended to undergo the full risk assessment whereas the second group may find it useful to undergo further testing as well. When determining inherited risk, the mother is not the only source of the genetic aberration, the father’s family history must be analyzed as well. Some confounding factors regarding risk assessment are adoption, young age at hysterectomy and oophorectomy, and families with few females. According to some, in patients who have these confounding factors and breast cancer before age 50 it may be appropriate to begin a genetic investigation. However, even with a positive family history, females younger than 21 should postpone testing as the negative psychological and emotional effects outweigh the potential benefits.

Table 2. Genetic risk assessment criteria.

20–25% risk of inherited predisposition to breast and ovarian cancer, testing recommended:	Personal history of both breast and ovarian cancer
	Ovarian cancer plus close relative with the same or premenopausal breast cancer
	Ashkenazi Jewish ancestry with ovarian cancer or breast cancer at <40years old
	Breast cancer at <50years old plus close relative with ovarian cancer
	Close relative with BRCA mutation
5–10% risk of inherited predisposition to breast and ovarian cancer, testing helpful:	Breast cancer <40years old
	Ovarian cancer, primary peritoneal, or fallopian tube cancer with high grade, serous histology
	Bilateral breast cancer
	Breast cancer <50years with close relative with breast cancer <50years old
	Ashkenazi ancestry with breast cancer <50years
	Breast cancer plus two close relatives or more with breast cancer
	Close relative matching any of the above scenarios

Modified with permission from ACOG Practice Bulletin Number 103.

It should be noted that patients with high-grade serous ovarian cancer, primary peritoneal, or fallopian tube cancer should be treated to a full genetic risk assessment as studies have recently shown that 16–21% will have a germline mutation in BRCA1 or BRCA2. The results of further testing may positively influence current patient care and the care of the closely related family.

4.1. Issues and testing 

During the genetic risk assessment counseling, all possible outcomes and their meanings (Table 3), the different methods for surveillance, chemoprevention, and surgery for risk reduction should be reviewed with the patient and appropriate family. Psychological issues will also be of great concern and patients should be offered support and resources in that area as well. In addition to the patient, the family must also be considered and there are some wonderful resources designed specifically for patient/family education. Materials such as pamphlets or websites can help communicate accurately to the patient and family the information regarding the disease itself and each member’s likely risks. Cost is an issue that is often forgotten and again there are resources that can inform and help patients with this issue. Fortunately, in the United States, much of the price of testing is covered by many insurance companies as well as Medicare. Worldwide, there is an increasing awareness, however, in many countries the patients themselves bear the costs of preventive medicine.

Table 3. Results of genetic testing to determine status of known cancer-causing mutation.

The discussion of laws is very important. In May, 2008, the Genetic Information Non-Discrimination Act known as GINA was signed into law by President George W. Bush. GINA is a groundbreaking federal law that protects US citizens from health insurance and employment discrimination based on their genetic information. Unfortunately, however, GINA does not prevent discrimination against the history of breast cancer disease itself. Some state insurance laws give additional protection and health insurance companies are not allowed to discriminate against a person based on his or her current health status.

Optimally, testing will begin with an affected individual. Both BRCA1 and BRCA2 genes will be fully sequenced because mutations can be found throughout the entire gene. Predictive testing using a single site test can be used once a mutation is identified. This method of testing, while initially time consuming and expensive, significantly decreases the total cost and time when multiple family members are involved. For testing of persons belonging to certain ethnic groups where founder mutations have been discovered these can be tested for initially with single site testing and will accrue less cost than fully sequencing both genes.

If no affected individual is available with whom to initiate testing, it is still possible and desirable to use a genetic test. When testing the unaffected individual, appropriate measures can be taken regarding screening and risk reduction if a mutation is noted. However, if no mutation is found then patients should be informed that this could be due to three possibilities. One, the patient did not inherit the mutation that runs in the family. Two, an unidentified mutation runs in the family and, therefore, it is not known if the patient is a carrier. And three, the family carries no genetic risk of cancer.

4.2. Risk reduction: ovarian and fallopian tube cancer 

Risk reduction strategies include surveillance, chemoprevention and surgery. Unfortunately current screening measures have a poor ability to detect ovarian cancer at an early and more treatable stage. Studies have shown that there is no reduced mortality or increased survival due to screening for ovarian cancer in high risk populations. However, the consensus is to continue screening intermittently starting at 30–35years of age or 5–10years earlier than the age ovarian cancer first occurred in the family. Current screening measures follow levels of CA-125 and make use of transvaginal ultrasound.

The use of oral contraceptives has not been shown to consistently reduce risk in high risk women. However, it does reduce risk in the general population and studies suggest that not only is long-term use of 3–6years effective but that any use of oral contraceptives provides benefits in risk reduction. In women with BRCA mutations, there is a suspicion as to whether the use of oral contraceptives increases risk of breast cancer. Importantly, parity has been shown to coincide with a reduced risk of ovarian cancer. These factors must be considered individually by the patient and her physician.

It is recommended to offer prophylactic salpingo-oophorectomy by 40years of age or upon completion of childbearing due to the poor ability of current screening procedures to identify early stage cancer. In addition to improving overall mortality, prophylactic surgery in women with mutations in BRCA1 or BRCA2 has shown a reduction in risk of 85–90% for primary ovarian, fallopian tube or peritoneal cancers.

4.3. Risk reduction: breast cancer 

Like risk reduction for ovarian cancer, risk reduction for breast cancer includes surveillance, chemoprevention and surgery. For surveillance, semiannual clinical breast examination plus annual mammography and annual breast MRI is the standard of care. This should begin at 25years or earlier depending on earliest age of onset in relatives. Use of tamoxifen in the general population has shown reductions in estrogen receptor positive breast cancer and early studies have shown that similarly, in women with BRCA2 mutations, tamoxifen reduces risk by a 62%. Due to the low occurrence of ER positive breast cancer in BRCA1 mutations, women with a BRCA1 mutation did not see benefits in risk reduction with tamoxifen use. Additionally, chemoprevention with raloxifene and aromatase inhibitors does not have current data to support their use.

A bilateral mastectomy for risk prevention surgery has shown to reduce risk by 90–95%. Total mastectomy achieves these numbers, however, partial mastectomy which preserves the nipple and areola has less of a success rate. If a woman with a BRCA mutation has previously had a mastectomy for breast cancer, it is appropriate to consider contralateral mastectomy due to the 30% incidence of contralateral cancer within 10years. This risk reducing surgery is not to be taken lightly. The psychological effects can be severe and the morbidity associated with the procedure can be high.

Due to the high estrogen receptor positive status in breast cancers of BRCA2 mutation carriers, prophylactic salpingo-oophorectomy confers a risk reduction of 40–70% for breast cancer. However, the benefits are seen only in premenopausal women and carriers of BRCA1 mutations could see less benefit, again, because of their low occurrence of ER positive breast cancer. Current research shows that short term use of hormone therapy does not significantly affect the risk reduction achieved by salpingo-oophorectomy.

4.4. Management without documented mutation 

Women with a strong family history of cancer but without a documented BRCA mutation still have a significant risk of breast cancer according to the current data. The data for risk of ovarian cancer is unclear. For these reasons, these women must be counseled according to their personal and family history. This risk is partially due to the limits of current technology in detecting all possible mutations is the BRCA genes. A close relationship with their physician is important because advances in surveillance technology may identify mutations that were previously hidden.

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5. Lynch syndrome 

In females, the most common malignancy of the genital tract is endometrial cancer (7), (8), (9). In 2005, there were approximately 40,000 cases in the US alone. Lynch syndrome or hereditary non-polyposis colorectal cancer (HNPCC) is to blame for approximately 2% of all endometrial cancers. In women younger than 50years, 10% of endometrial cancer is due to Lynch syndrome. While Lynch syndrome is known to cause colorectal cancer it also causes cancer of the small bowel and stomach, ovarian and endometrial cancer, hepato-biliary, renal, and brain cancers.

Inherited by autosomal dominance, Lynch syndrome is caused by a germline mutation in one of the DNA mismatch repair (MMR) genes including MLH1, MLH3, MSH2, MSH6, PMS1, and PMS2. Its prevalence in the population is estimated to be 1 in 660–2000 which corresponds to 0.3–5.8%. Patients with Lynch syndrome have most often inherited a germline mutation in one allele that puts them at risk for a subsequent second-hit in the other allele. Research has indicated that a majority of cases of Lynch syndrome are caused by the loss of MSH2 or MLH1 while MSH6 mutations are responsible for about 15% of cases. Onset of brain and hematologic cancers in childhood secondary to Lynch syndrome is the result of loss of both MMR alleles in the offspring of two parents with Lynch syndrome.

The phenotype of Lynch syndrome varies depending on several factors such as gender and race. There are certain genotype-phenotype effects that are known. MSH2 and MLH1 mutations carry a 50–70% risk of colorectal cancer (CRC) and for endometrial cancer the risks are 40% for MSH2 mutations, 27% for MLH1 mutations, and 70% with MSH6 mutations. Whether or not it is more common for it to present as endometrial cancer than colorectal cancer in women is still debated as there is evidence that supports both positions. In up to 61% of those with Lynch syndrome an additional primary cancer is found in those with endometrial cancer. Also, in those with two primary cancers the sentinel cancer was often endometrial or ovarian. Because of this it is extremely important to screen gynecologically in addition to colorectally.

Lynch syndrome carries a risk of ovarian cancer of 10–12% with MSH2 carriers having a risk of 36% over their lifetime. The average age of diagnosis was around 42years with a 69% 5year survival rate. There is some data present to suggest that there is a difference in the clinical presentation between BRCA associated ovarian cancer and ovarian cancer in HNPCC. This data shows that approximately two thirds of HNPCC ovarian cancers were stage I and II with an average age of diagnosis at 42–49years. More research is needed to determine if the clinical presentation is indeed distinct from BRCA associated ovarian cancer as screening and prophylactic surgery could be affected.

5.1. Diagnosis of lynch syndrome 

Identifying patients at risk for HNPCC-related ovarian and endometrial cancer was previously done using a combination of family history and clinical criteria known as Amsterdam criteria-I. However, this method excluded extra-colonic malignancies, which prevented the identification of a significant amount of mutation carriers. The criteria were updated to include extra-colonic manifestations and now comprise Amsterdam criteria-II, which have a sensitivity and specificity of 78% and 61%, respectively. Currently, Bethesda criteria have been created that have sensitivity at 94% but decreased specificity at 25%. By using only the first three criteria in the Bethesda criteria, specificity is improved up to 49%.

The Bethesda criteria are used as a first step in diagnosing Lynch syndrome to select patients for further screening using molecular techniques. Direct DNA MMR gene analysis may be used for those with a strong family history of Lynch syndrome or if tumor analysis is unavailable or inconclusive. A positive test will confirm Lynch syndrome while a negative test, like testing for BRCA mutations, does not rule out the possibility of malignancy.

Molecular testing of tumors involves immunohistochemistry (IHC) studies and identifying regions of microsatellite instability (MSI). Currently there is no opinion on which should be performed first. However, cost-saving measures would have IHC performed first on patients meeting strict clinical criteria and likely have mutations in already identified genes. MSI studies can then be done with those meeting the revised Bethesda criteria to search for the possibility of affected regions not identified with mutations yet.

Molecular testing of gynecological cancers has its limitations. Identical mutations can show remarkably different patterns of MSI in CRC vs. endometrial cancers while IHC may miss 70% of certain mutation carriers. In addition, not all tumors show significant amounts of MSI. A combination of both analyses is best for detecting the mutation type. Moreover, population studies suggest that the Amsterdam and Bethesda criteria are not as sensitive as once thought. Several risk prediction models have been developed (Amsterdam-plus, PREMM, MMRpro, etc) and appear to perform equally or better than Amsterdam and Bethesda criteria. However, continual research and improvement is necessary to determine the best risk model to use and ultimately to provide the most accurate surveillance results.

5.2. Screening 

Screening for endometrial cancer consists of endometrial sampling or biopsy (EMB) and transvaginal scans (TVS) starting between ages 30–35. Some early data have suggested that endometrial hyperplasia contains MSI whereas normal endometrium does not and the natural history of endometrial cancer is that it can be preceded by hyperplasia and abnormal bleeding. Due to the limits of current screening, it is hoped that in the future DNA screening will prove to be an affordable and accurate screening method. Currently, screening those with Lynch syndrome for endometrial cancer has not proven useful. Because endometrial cancer presents at an early stage and has a good prognosis, therefore, it is unknown if screening would improve outcome significantly.

Like screening for endometrial cancer, screening for ovarian cancer in Lynch syndrome has no proven efficacy. In spite of this, many women choose surveillance over surgery. This may be from a desire to maintain fertility in younger women, to prevent premature menopause in all women, or opposition to. There are currently trials in the UK and the US evaluating whether screening every three or four months is more effective than annual screening.

5.3. Prevention 

The use of oral contraceptive pills (OCPs) has shown effectiveness in preventing endometrial and ovarian cancer in BRCA mutation carriers and in the general population but a slight increase in breast cancer rates has been seen with OCP use. The effectiveness of OCPs in Lynch syndrome does not yet have supporting data. Therefore use of OCPs should be decided by the patient and her physician after carefully weighing all available information.

Treatment of atypical endometrial hyperplasia and endometrial cancer has been accomplished with progestrogens. The Mirena device, an intrauterine contraceptive, has shown success in endometrial suppression and regression of hyperplasia and even reversal of the endometrioid type of endometrial cancer. It must be said that there have been instances, however, where endometrial cancer has occurred despite the current use of Mirena.

Prophylactic total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO) has shown remarkable results with no women developing endometrial or ovarian cancer afterwards. Thirty three percent of women with Lynch syndrome who did not elect to have prophylactic surgery developed endometrial cancer and 5–6% developed ovarian cancer. Therefore, due to the fact that screening does not have supporting data, it is recommended to screen annually and undergo prophylactic surgery by 40years of age. In addition to prophylactic surgery, women should undergo hormone replacement therapy until age 51 due to the increased mortality from surgical menopause before age 45.

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6. Unopposed estrogen stimulation and endometrial cancer 

The cells of the endometrium respond to estradiol by stabilizing and proliferating while the effects of progesterone cause them to stop growing and to differentiate. The interactions of estradiol and progesterone during the menstrual cycle are responsible for the waxing and waning of endometrial tissue and the ability of the uterus to sustain a pregnancy. At the end of the cycle the withdrawal of estradiol and progesterone causes the destabilization and sloughing of the endometrium. During the next cycle, estradiol will again cause the stabilization and proliferation of the endometrium from the base of the tissue remaining after menses.

6.1. Screening 

This cycle of estradiol and progesterone is essential not just for fertility but in maintaining normal pathophysiology of the endometrium. Constant stimulation of the endometrium by estradiol, without opposition from progesterone, leads to endometrial hyperplasia. This hyperplasia can then lead to development of type I endometrial cancer also known as estrogen dependent. Also known as endometrioid adenocarcinoma this is the most common type of endometrial cancer and generally the mildest. Prevention and screening for this type is relatively straightforward since the etiology is due to conditions of estrogen excess without progesterone opposition.

Several acquired mutations have been identified in type I endometrial cancer. These mutations have been found in genes for PTEN, k-ras and beta-catenin and are considered to play early roles in the development of endometrial cancer. Microsatellite instability has also been found. Mutations in PTEN, which is the most common mutation, has two functions related to a lipid and protein phosphatase. The lipid phosphatase functions in cell cycle arrest while the protein phosphatase is involved with inhibiting cell spread, migration, and growth factor stimulated pathways. This can cause individual cells to become overly sensitive to the normal levels of estrogen while at times the cell itself will overexpress the estrogen receptor gene. K-ras mutations are suspected to be involved in the malignant potential of tumors without the prerequisite of hyperplasia. Lastly, beta-catenin is a part of a subtype of cadherin proteins and is necessary for differentiation, signal transduction and normal cell/tissue structure.

6.2. Treatment 

Though endometrioid adenocarcinoma often has a good prognosis, benign and malignant squamous differentiation can be found alongside adenocarcinoma. The prognosis is determined solely by the glandular component and takes into account myometrial invasion and glandular and nuclear differentiation. The precursor lesion to endometrioid adenocarcinoma is hyperplasia of the endometrium. The stages of endometrial hyperplasia are difficult to separate histologically and there are several classification systems. It is important to note that atypical endometrial hyperplasia not only advances to cancer but that it is often found along with previously undetected uterine cancer.

According to ACOG, atypical endometrial hyperplasia is considered part of a continuum with endometrial cancer and the true diagnosis will always be questionable without the removal of the uterus. Therefore, it is recommended that a hysterectomy be done in women who do not wish to remain fertile and who also have atypical endometrial hyperplasia. However, in women with atypical endometrial hyperplasia or grade I endometrioid adenocarcinoma, progestins may be used to slow or reverse the disease process. Response rates to progestin therapy range from 58% to 100% and therapy may be delivered orally, parenterally, or by intrauterine device. After fertility is no longer desired, patients should be recommended to undergo hysterectomy as recurrence and progression of disease are highly likely.

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7. Is there a place for IVF, IVF–ET and PGD in prevention of breast cancer 

It is remarkable that the initial intent of the pioneer of in vitro fertilization and in vitro fertilization–embryo transfer (IVF–ET), Professor Robert Edwards was to prevent genetic diseases, particularly cancer through preimplantation genetic diagnosis (PGD) (10). Although PGD was first reported more than thirty years ago by Robert Edwards when they managed to identify the sex of rabbit blastocysts, it was not until later in the 1980s when PGD of human embryos was extensively investigated (11). In 1990, Alan Handeyside reported the birth of healthy females after sex selection using polymerase chain reaction (PCR) to amplify a Y chromosome, a repeat sequence, to exclude male embryos (12). There is a wide range of single gene disorders that could be screened for using PGD and the number of such diseases has been growing exponentially in the last few years. According to the European Society for Human Reproduction and Embryology (ESHRE), PGD consortium data, the most common autosomal recessive disease are cystic fibrosis beta thalassemia and spinal muscular dystrophy (13), (14). The most common autosomal dominant diseases include myotonic dystrophy, Huntington disease, neurofibromatosis and adenomous polyposis coli. Although screening for familial breast cancer is technically possible, in practice, there has been very limited clinical experience available. Perhaps, as younger generations are screened rather than affected patients only, PGD screening for cancers might be more utilized in the future.

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8. Conclusion 

We are at the dawn of genetic screening for cancers. It might appear that there has been remarkable advances in terms of our understanding of the genetic origin of cancer. In reality however, even in the post era of the human genome project, there has been minimal advances in this wide open arena for disease understanding and prevention. Medicine always lags behind science and technology and this is where there might be some hope for the future.

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