Showing posts with label RRSO. Show all posts
Showing posts with label RRSO. Show all posts

Wednesday, April 27, 2016

Elective oophorectomy or ovarian conservation at the time of benign hysterectomy?


Hysterectomy is the second most common surgery performed in US after cesarean section.  According to CDC data approximately 600,000 hysterectomies are performed each year. A nationwide study further reported that unilateral or bilateral oophorectomy was performed in 68 percent of women at the time of abdominal hysterectomy, 60 percent at laparoscopic hysterectomy, and 26 percent at vaginal hysterectomy.

Women have an option of undergoing elective oophorectomy (EO) along with benign hysterectomy to reduce the risk of ovarian cancer, thereby reducing a chance of second surgery coupled with decreased perceived   anxiety of breast and ovarian cancer subsequently.But there are negative side effects of this surgical induced menopause such as death, total cancer mortality, osteoporosis, cognitive decline, decreased sexual drive and increased cardiac mishap support conservation of ovarian function.

There is considerable debated going on between EO and ovarian conservation, with strong statements are put forward in favor of each. Currently ACOG recommends “strong consideration should be made for retaining normal ovaries in premenopausal women who are not at increased genetic risk of ovarian cancer. [However,] given the risk of ovarian cancer in postmenopausal women, ovarian removal at the time of hysterectomy should be considered for these women.”

Arguments in favor of ovarian conservation:


  • EO is detrimental for the overall health of women and decreases the life expectancy due to coronary artery disease. In a landmark study by Parker et al using Surveillance, Epidemiology, and End Results (SEER) database, the National center for Health Statistics, the Women’s Health Initiative, and the National Inpatient Sample it was seen that there is no clear cut benefit of EO at any age and women died early due to associate morbidity.
  • The neuroprotective benefits of estrogen were seen in multiple studies and was further supported by declining cognitive functions specially in women undergoing EO under 50 yrs.
  • EO leads to increase in hip fracture due to decrease in BMD as estrogen levels plummet. This was specifically seen in the light of mass discontinuation of hormone replacement therapy among postmenopausal women when results of Women’s Health Initiation trial published.
  • A decrease in sexual desire and function, resulting in quality of life issues and conflict in interpersonal relationship, depression was seen after oophorectomy.

Arguments in favor of EO:


  • Ovarian cancer is the fifth leading cause of death among women in US with estimated 22,280 new cases and  14,240 deaths in 2016. A woman’s lifetime risk of ovarian cancer is 1 in 70 or 1.4% with no known effective screening method that could diagnose it at very early stage. Researchers have estimated   that 1000 new cases of ovarian cancer could be avoided if EO is performed in women undergoing hysterectomy in women 40 years and older.
  • In women at high risk for ovarian cancer (especially with familial history or genetic predisposition, BRCA1 or BRCA2 mutations) risk-reducing oophorectomy (RRO) reduced cancer specific mortality.
  • In general population RRO is an ideal treatment for the prevention of ovarian cancer in women who have known risk factors like being white, never having been pregnant, late age of menopause, and a long estimate number of years of ovulation in absence of effective screening strategies.
  • EO leads to avoiding the risk of second surgery after hysterectomy due to adnexal disease or masses.
  • Effective replacement therapy available to prevent osteoporosis, cardiac and sexual dysfunctions is being put as a valid argument in support of EO, specifically after the beneficial results of hormone therapy from Women’s Health Initiative studies.
  • A recent study by Trabuco et al published in the May issue of Obstetrics and Gynecology has concluded that even if ovaries are spared at the time of hysterectomy, it affects the ovarian reserve as evident by declining levels of Antimüllerian hormone. The study also reported that women undergoing hysterectomy became menopausal 1.9 years earlier than referent patient who has not undergone any surgery.


Despite all these arguments studies have recently documented that of all the hysterectomies performed for benign reason 36%-38% were deemed unnecessary and histologically normal.

So, the decision for EO should be made according to each woman’s individual genetic test results and her risk for developing ovarian malignancy. Age at the time of benign hysterectomy is an important decisive factor. In 2010, recommendations from the Society of Gynecologic Oncologists state “Ovarian conservation before menopause may be especially important in patients with a personal or strong family history of cardiovascular or neurological disease. Conversely, women at high risk of ovarian cancer should undergo risk-reducing bilateral salpingo-oophorectomy.”

A women’s risk of cardiovascular disease, dementia, osteoporosis, and family history must be taken into account before decisions for EO or ovarian conservation are made in woman considering hysterectomy.



References:
http://journals.lww.com/greenjournal/Fulltext/2016/05000/Association_of_Ovary_Sparing_Hysterectomy_With.3.aspx


Tuesday, April 5, 2016

The NCCN add new inherited genetic mutations that are linked to ovarian and breast cancer.




The National Comprehensive Cancer Network (NCCN) has implicated several additional mutations when planning risk management strategies in patients with hereditary breast and ovarian cancer. These mutations confer a risk of either or both cancers with relatively high penetrance.

Dr. Tuya Pal  MD, from the Moffitt Cancer Center, Tampa, Florida said “ the recent discovery that the genetic mutation PALB2 is associated with an aggressive form of breast cancer, as well as the realization that the newer ovarian cancer genes RAD51C, RAD51D, and BRIP1 pose an added lifetime risk for ovarian cancer, should prompt physicians to discuss possible prophylactic procedures with patients who are found to carry these mutations” at 21st Annual National Comprehensive Cancer Network (NCCN) conference in Hollywood, FL.

It is known that women who have BRCA1 carriers have a 55 to 65 percent chance of developing breast cancer and 35 to 70 % chance of developing ovarian by age 70 and the corresponding numbers for BRCA2 carriers are 45% and 10-30% respectively. Women with Lynch syndrome have around 10% chance of developing ovarian cancer. The researchers at the conferences implicated additional mutation BARD1, BRIP1, RAD51C, RAD51D and PALB2 with similar level of evidence as BRCA1/2 for ovarian cancer.

Together with established Ovarian Cancer (OC) genes, this addition bring the total number of genes suspected to cause hereditary OC to 11.

Till now, the NCCN was advising or recommending risk reduction surgery of salpingo-oophorectomy as a part of preventive strategy in BRCA1/2 mutation carrier. According to National Cancer Institute( NCI) the lifetime risks of ovarian cancer are 5.2% in RAD51C mutation carriers, 5.8% in BRIP1 mutation carriers, and 12% in RAD51D mutation carriers; risk-reducing salpingo-oophorectomy (RRSO) may be considered for these patients upon completion of childbearing. 

Genes such as CHEK2 and ATM are associated with a 20% or higher lifetime risk of breast cancer; similarly, genes such as RAD51C, RAD51D, and BRIP1 are associated with a 5% to 10% risk of ovarian cancer; many of these genes are now included on multi-gene panels, although the clinical actionability of these findings remains uncertain and under investigation.

Screening for these genes is specifically important in regards to Ovarian cancer as there are no screening test and diagnostic modalities at present to catch the disease at an early stage.

A family history should always be taken into account and with strong family history; prophylactic risk management in the form of oophorectomy should be considered.

PALB2 is also an important genetic mutation added to the list along with PTEN, and PT53 that causes the Breast cancer. Women with an abnormal PALB2 gene have a 14% risk of developing breast cancer by age 50 and a 35% risk of developing breast cancer by age 70. It is also seen that cancers developing in patients with the genetic mutation PALB2   are very aggressive and in a polish study  survival for women with breast cancer and a PALB2 mutation was 48·0% compared with 74·7% for patients without a mutation.

So, genetic testing at this point of time has become an important part of cancer management, because if we are proactive we can diagnose the cancer at very early stage or prevent it altogether if we know our risk for them.

Much progress has been made in the field of genetic testing with increased use of multi-gene testing. Genetic testing allow the patients to make an informed decision, about there course of treatment, prognosis and any other cancer risks due to genetic mutation.

The updated NCCN Guidelines for Women with Mutations in PALB2, ATM, CHEK2, BRIP1, RAD51C, and RAD51D

1) Breast Cancer Screening:
Annual MRI beginning at age 30 or earlier, based on family breast cancer history for women with mutations in following genes: ATM, CHEK2 and PALB2

2) Breast Cancer Risk Management
Discussing the option of risk-reducing mastectomy for women with mutations in: PALB2

3) Ovarian Cancer Risk Management
Women with mutations in following genes should consider risk-reducing removal of ovaries and fallopian tubes: BRIP1, RAD51C and RAD51D.

References:
Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population JCO (2015) 33 (26): 2901-2907