Health Occupations

Period 2B

Genetic Susceptibility to Cancer in Women and Surgeries to Prevent these

Cancers
Reproductive (most notably ovarian and endometrial) and breast cancers are amongst the
most commonly diagnosed cancers in women. There were an estimated 232,670 new cases of
breast cancer and 94,990 new cases of genital system cancer diagnosed in women during 2014
within the United States; along with estimated deaths of 40,000 from breast cancer and 28,790 of
genital system cancer (Siegal et al, 10). Women may also have a higher genetic susceptibility to
some types of cancer. Most commonly known genetic mutations that may raise susceptibility to
breast and ovarian cancer are of the BRCA1 and BRCA2 genes. However, there are also other
gene mutations that have been proven to cause breast and ovarian cancer. For example, in a study
by Lindsey Minion and colleagues, 19 mutations were found to possibly increase the
susceptibility to ovarian and breast cancer. (86-92) Additionally, Lynch Syndrome (hereditary
nonpolyposis colorectal cancer) can raise the chance of developing cancer, especially ovarian
and endometrial cancers in women.
Some women that learn that they have a genetic proneness to reproductive or breast
cancer elect to have prophylactic surgery to lower their risk of developing cancer. These
surgeries may include: a prophylactic mastectomy (removal of one or both breasts), a salpingooophorectomy (the removal of the fallopian tube [salpingectomy] and ovary [oophorectomy])
and hysterectomy (removal of the uterus). These surgeries have been brought to the attention of
the public recently mainly by Angelina Jolie Pitt, who carries the BRCA1 gene mutation. After I
heard Jolies story in 2013 I became increasingly interested in learning more about cancer and
why people develop it. Her story about the genetic susceptibility to breast and reproductive

cancers fascinated me and fueled my interest in going into a medical field-- specifically going
into gynecology or oncology. So naturally when I came across Jolies story again this year, I
choose to write about breast and reproductive cancer susceptibility and the surgeries that some
women elect to help lower their risk. Jolie-Pitt elected to have a prophylactic double mastectomy
and a salpingo-oophorectomy, but chose not to have a hysterectomy. She wrote two OP-EDs in
the New York Times, explaining that she had grim family history with breast and reproductive
cancers and that she had an estimated 87% chance of developing breast cancer and a 50% chance
of developing ovarian cancer (Jolie Pitt).
Although the celebrity had two preventive surgeries, some physicians question the
necessity of the surgery among varying cases. A mastectomy removes the ability to breastfeed
from the removed breast. It also causes loss of sensation in the breast and yet, the surgery only
reduces the risk of developing cancer by 90%. A salpingo-oophorectomy in premenopausal
women causes surgically induced menopause, which can causes problems with the sudden
hormone imbalance and only reduces the cancer risk 80-90%. Some medications can help with
the imbalance. However, side effects vary greatly with different patients. A hysterectomy is a
fairly low risk surgery but it can cause early onset menopause and possible vaginal prolapse.
Though there are risks and side effects of each surgery, I believe that the benefits outweigh the
costs for women at a high genetic risk of developing breast and gynecologic cancer.
Women with a substantial family history of breast and/or gynecologic cancers are more
likely to carry the BRCA1 and/or BRCA2 mutations (Both BRCA1 and BRCA2 are transmitted
as autosomal dominant trait) and are often urged by their physicians to get tested for the
mutation. With the next generation sequencing, hereditary panel testing is an efficient method for
evaluating genes and has considerably dropped in price over time. If women are found to be a
carrier of this gene, physicians educate the patient about all of her lifetime risks, possible
treatments, and preventative surgeries that she could undergo. Women with BRCA1 or BRCA2

mutations have a 60 to 85% cumulative lifetime risk (to 70 years of age) of invasive breast
cancer and a 15 to 65 % cumulative lifetime risk of invasive epithelial ovarian cancer (Kauff et
al). As a preventative measure, women with BRCA1 and BRCA2 mutations have the option to
have hormone therapy as chemoprevention, in the form of the oral contraceptive (either
combined estrogenprogesterone or medroxyprogesterone). The estimated reduced risk of
ovarian cancer in carriers of BRCA1 and BRCA2 mutations is about 44-61% (Osman).
Additionally, physicians may be more likely to urge chemoprevention combined with regular
screenings to BRCA2 positive patients, rather than a carrier of the BRCA1 mutation or both
genetic mutations, because it is proven to be associated with a better response to the treatment.
Patients with the BRCA1 and BRCA2 mutations may also elect to get more frequent screening
and testing. This method is generally ineffective in preventing breast and reproductive cancers.
Methods to screen for reproductive cancers include: transvaginal ultrasound examinations and
the CA 125 blood test (a test that measures the amount of the cancer protein, CA 125, or cancer
antigen in your blood). Both methods often miss the early signs of the disease and often do not
detect it until the disease has progressed (Osman). For breast cancer screening, physicians
recommend frequent self exams and mammograms, which often do detect the early signs of
cancer. Next physicians may suggest a preventive surgery. In Kauffs study: We evaluated 170
women with germ-line BRCA mutations who elected either risk-reducing salpingooophorectomy or surveillance for ovarian cancer. The projected cancer free percentage in each
group: 94 percent in the salpingo-oophorectomy group and 69 percent in the surveillance group.
(et al) These results provide strong support for the risk-reducing salpingo-oophorectomy as part
of a preventiveoncology strategy for women with a BRCA1 or BRCA2 mutation. However, the
surgery does not erase the risk of cancer for women with the BRCA1 and BRCA2 gene
mutations. Carriers of BRCA 1 and BRCA2 mutations who underwent prophylactic salpingooophorectomy developed peritoneal cancer even after prophylactic surgery. However, the
mortality reduction associated with this surgery is substantial.(Domchek et al, 969) Peritoneal
cancer is a rare malignancy that develops in the peritoneum, a membrane that lines the inside
wall of the abdomen and covers the uterus and extends over the bladder and rectum. Peritoneal
cancer acts much like ovarian cancer and women with the BRCA1 and BRCA2 mutations and
are also more susceptible than the general population to this camcer. In a study by Domchek,
risk-reducing mastectomy was associated with a decreased risk of breast cancer in BRCA1/2

mutation carriers; because no breast cancer events were seen in women who underwent riskreducing mastectomy during three years of prospective follow-up. In contrast, 7% of women
without risk-reducing mastectomy over a similar follow-up period were diagnosed with breast
cancer (969). In short, the preventive surgeries for women with a higher genetic susceptibility
have more benefits than costs.
Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is
a type of inherited cancer of the digestive tract, but is also known to increase the chances of
getting ovarian, endometrial, and breast cancer amongst women with the disease. Mutations of
several genes including MLH1, MSH2, MSH6, PMS2, and EPCAM are associated with Lynch
Syndrome. Lynch Syndrome accounts for another 10% to 15% risk for developing genetic
ovarian cancer (Schmeler et al). Women with Lynch Syndrome can also be offered
chemoprevention using the oral contraceptive (either combined estrogenprogesterone or
medroxyprogesterone) with a 50% reduction rate for endometrial cancer susceptibility (Osman).
Patients with Lynch Syndrome may also elect to get more frequent screening and testing.
Current screening guidelines for gynecologic cancer recommend annual pelvic examinations,
transvaginal ultrasonography, endometrial biopsy, and measurements of serum CA-125 levels
beginning at 25 to 35 years of age (Schmeler et al). This method is generally ineffective in
preventing breast and reproductive cancers with patients with Lynch Syndrome as well as being
under-researched. (Osman). As for breast cancer screening with patients with Lynch Syndrome it
is the same as with the BRCA-mutation patients, physicians recommend frequent self-exams and
mammograms. These self-examinations often do find the early signs of cancer, but do not lower
the risk of developing cancer, rather they lower the mortality rate. As for surgeries for patients
with Lynch Syndrome, less research has been conducted, but physicians may advise patients to
undergo a prophylactic hysterectomy and salpingo-oophorectomy to lower the risk of
endometrial and ovarian cancer. In a study conducted by Schmeler, This study provides

evidence of a benefit of prophylactic hysterectomy and bilateral salpingo-oophorectomy in

preventing gynecologic cancers in women with Lynch Syndrome. In our cohort, there were no
new cases of endometrial or ovarian cancer among the women who underwent prophylactic
surgery. This is a significant conclusion because research is extremely limited in this area.
Women with Lynch Syndrome are not usually advised to have a mastectomy, unless they have a
family history of breast cancer. Instead they are advised to monitor if symptoms arise (Osman).
Women with Lynch Syndrome have a genetic susceptibility to many types of cancer, thus the
safe monitoring is recommended rather than undergoing invasive surgery. Although, data is
conclusive that prophylactic hysterectomy and salpingo-oophorectomy are beneficial to
preventing endometrial, ovarian, breast, and peritoneal cancer (Osman) (Schmeler et al).
Before starting research for this paper I had only heard about Angelina Jolie Pitts story
with the BRCA1mutation and her double mastectomy. I had never heard the word salpingooophorectomy, or truly realized the risks, options and complications a person with BRCAmutations or Lynch Syndrome faced. Although research is not abundant about Lynch Syndrome
patients undergoing preventive surgeries, the research paper I consulted concluded that advising
these patients to undergo such surgeries is beneficial (Schmeler et al). For BRCA1 and BRCA2
mutations however, I learned much more because of the extensive research done in this area.
Personally I think this is ideal because of how commonly breast and reproductive cancers are
diagnosed in women. This paper also further inspired me to continue researching gynecology and
oncology as a future career fields.

Works Cited
Domchek, Susan M. MD; Tara M. Friebel, MPH; Christian F. Singer, MD, MPH; D. Gareth Evans, MD; Henry T.
Lynch, MD; Claudine Isaacs, MD; Judy E. Garber, MD, MPH; Susan L. Neuhausen, PhD; Ellen Matloff,
MS; Rosalind Eeles, PhD; Gabriella Pichert, MD; Laura Van tveer, PhD; Nadine Tung, MD; Jeffrey N.
Weitzel, MD; Fergus J. Couch, PhD; Wendy S. Rubinstein, MD, PhD; Patricia A. Ganz, MD; Mary B.
Daly, MD, PhD; Olufunmilayo I. Olopade, MD; Gail Tomlinson, MD, PhD; Joellen Schildkraut, PhD;
Joanne L. Blum, MD, PhD; Timothy R. Rebbeck, PhD "Association of Risk-Reducing Surgery in BRCA1
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Minion, Lindsey E., Jill S. Dolinsky, Dana M. Chase, Charles N. Dunlop, Elizabeth C. Chao, and Bradley J. Monk.
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