Bilateral Salpingo‐Oophorectomy

• Risk‐reducing bilateral salpingo‐oophorectomy (RRBSO) – or the removal of fallopian tubes and ovaries:
  • Is the advised surgical prophylaxis for hereditary breast and ovarian cancer (HBOC) mutation carriers
• Other preventive and cancer screening measures available for these women:

Bilateral Salpingo‐Oophorectomy

• Risk‐reducing bilateral salpingo‐oophorectomy (RRBSO) – or the removal of fallopian tubes and ovaries:
  • Is the advised surgical prophylaxis for hereditary breast and ovarian cancer (HBOC) mutation carriers
• Other preventive and cancer screening measures available for these women:
  • Such as serial CA125 levels and pelvic ultrasounds:
    • Have not been shown to reduce cancer mortality in this high‐risk population
• RRBSO has been associated with significantly improved cancer‐specific mortality:
  • For ovarian, fallopian tube, peritoneal and breast cancers, as well as improved all‐cause mortality in BRCA carriers
• In a multicenter, prospective study of 2482 women with a known BRCA1 or BRCA2 mutation:
  • Women treated with RRBSO had a:
    • Decreased ovarian cancer risk (1% vs 6%)
    • Decreased breast cancer risk (2% vs 6%)
    • Improved all‐cause mortality (3% vs 10%)
• Retrospective data supports the relative risk of gynecologic cancer:
  • After RRBSO to be 0.04 (95% CI, 0.01‐0.16)
  • In that study, only 2 of 253 women who underwent RRBSO were later diagnosed with peritoneal carcinoma:
    • 58 women out of 292 matched controls received a diagnosis of the ovarian, fallopian tube, or peritoneal cancer after a mean follow up of 8.8 years
• In a prospective study which controlled for history of prophylactic mastectomy:
  • The hazard ratio for the diagnosis of breast cancer or gynecologic cancer in a patient with BRCA after RRBSO was 0.25 (95% CI, 0.08‐0.74)
• As more recent data have supported that many ovarian cancers may originate within the fallopian tube:
  • There are currently ongoing studies exploring whether bilateral salpingectomy alone is an effective risk‐reducing procedure
• Generally, BRCA‐positive women elect to defer RRBSO:
  • Until they complete their childbearing
• Age‐related risk, however, differs between BRCA1 and BRCA2 carriers:
  • BRCA1 carriers are at an elevated lifetime risk for ovarian cancer compared to BRCA2 carriers and are also more likely to develop it earlier in life:
    • Specifically, women with BRCA1 mutations have an:
      • Average age at ovarian cancer diagnosis of 50 years
      • A significantly increased ovarian cancer risk starting at 35 years:
        • Which continues to increase with age
  • Women with BRCA2 mutations:
    • Have an average age of ovarian cancer diagnosis of 60 years
    • A significantly increased ovarian cancer risk starting at 50 years:
      • Which then plateaus at a 14% risk
    • Therefore, BRCA2 carriers may elect to defer RRBSO to a later age compared with BRCA1 carriers:
      • However, if they choose to do so, they must be counseled that they may not receive the benefit of decreased breast cancer risk after RRBSO
• Nevertheless, the society of Gynecologic Oncology (SGO):
  • Continues to recommend that BRCA1 and BRCA2 mutation carriers:
    • Undergo RRBSO after completing childbearing or by age 35 to 40 years
• Thorough preoperative counseling is critical in helping patients decide whether to proceed with RRBSO:
  • RRBSO is generally performed laparoscopically and is a low‐risk procedure:
    • The reported complication rate (both major and minor) of RRBSO:
      • Has been quoted as 4% but is even lower at high volume institutions
  • In addition, patients must be advised that there is a 4% to 8% risk of discovering an occult malignancyeither at the time of RRBSO or on final pathology
  • Preoperative serum CA125 should be obtained and patients should undergo a pelvic ultrasound
  • Patients should be consented for ovarian cancer staging surgery in case visible disease is seen and counseled that an occult malignancy may be detected on final pathology, thus requiring additional surgery
  • Women should also be counseled that at the time of RRBSO they will undergo surgical menopause and may begin to experience hot flashes, mood changes, vaginal dryness, dyspareunia, decreased libido, osteoporosis, cardiovascular disease, and possible impaired cognitive function:
    • Although surgical menopause before age 45:
      • Has been associated with increased overall mortality in the general population, this risk must be balanced with the substantially decreased all‐cause mortality after risk‐reducing surgery for the high‐risk HBOC population
    • Nonhormonal agents should be used as a first‐line therapy for these symptoms:
      • But hormonal replacement therapy (HRT) is also likely safe on the basis of a recent study of almost 900 postoophorectomy BRCA1 mutation carriers:
        • In that prospective longitudinal study, investigators found that HRT use was not associated with an increased risk of breast cancer (HR 0.97, 95% CI, 0.62‐1.52, P = .89)
        • However, when analyzing only women who used HRT:
          • The incidence of breast cancer was lower with estrogen‐only HRTcompared with combination estrogen and progesterone (12% vs 22%, log‐rank P = .04)
          • Estrogen‐only HRT is only recommended for women who have undergone a hysterectomy, as without progesterone support, it significantly increases the risk for endometrial cancer in the general population
        • A recent meta‐analysis including three trials with 1100 patients also demonstrated there was not a significantly higher breast cancer risk associated with HRT after RRBSO in BRCA1 and BRCA2 mutation carriers (HR 0.98, 95% CI, 0.63‐1.52)
        • Nevertheless, the relationship between HRT and individual all‐cancer risk is complex and imperfectly understood at this time
        • The results of long‐term, prospective studies are necessary to draw more definitive conclusions in this high‐risk population
• References:
  • Domchek SM, Friebel TM, Singer CF, et al. Association of risk‐ reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967‐975. 
  • Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophor- ectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346(21):1616‐1622. 
  • Kauff ND, Satagopan JM, Robson ME, et al. Risk‐reducing salpingo‐ oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346(21):1609‐1615. 
  • Antoniou A, Pharoah PDP, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117‐1130. 
  • Manchanda R, Abdelraheim, Johnson M, et al. Outcome of risk‐ reducing salpingo‐oophorectomy in BRCA carriers and women of unknown mutation status. BJOG. 2011;118(7):814‐824. 
  • Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ. Survival patterns after oophorectomy in premenopausal women: a population‐based cohort study. Lancet Oncol. 2006;7(10):821‐828. 
  • Kotsopoulos J, Gronwald J, Karlan BY, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncology. 2018;4(8):1059. 
  • Marchetti C, De Felice F, Boccia S, et al. Hormone replacement therapy after prophylactic risk‐reducing salpingo‐oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a meta‐ analysis. Crit Rev Oncol Hematol. 2018;132:111‐115. 

• Such as serial CA125 levels and pelvic ultrasounds:
  • • Have not been shown to reduce cancer mortality in this high‐risk population
• RRBSO has been associated with significantly improved cancer‐specific mortality:
  • For ovarian, fallopian tube, peritoneal and breast cancers, as well as improved all‐cause mortality in BRCA carriers
• In a multicenter, prospective study of 2482 women with a known BRCA1 or BRCA2 mutation:
  • Women treated with RRBSO had a:
    • Decreased ovarian cancer risk (1% vs 6%)
    • Decreased breast cancer risk (2% vs 6%)
    • Improved all‐cause mortality (3% vs 10%)
• Retrospective data supports the relative risk of gynecologic cancer:
  • After RRBSO to be 0.04 (95% CI, 0.01‐0.16)
  • In that study, only 2 of 253 women who underwent RRBSO were later diagnosed with peritoneal carcinoma:
    • 58 women out of 292 matched controls received a diagnosis of the ovarian, fallopian tube, or peritoneal cancer after a mean follow up of 8.8 years
• In a prospective study which controlled for history of prophylactic mastectomy:
  • The hazard ratio for the diagnosis of breast cancer or gynecologic cancer in a patient with BRCA after RRBSO was 0.25 (95% CI, 0.08‐0.74)
• As more recent data have supported that many ovarian cancers may originate within the fallopian tube:
  • There are currently ongoing studies exploring whether bilateral salpingectomy alone is an effective risk‐reducing procedure
• Generally, BRCA‐positive women elect to defer RRBSO:
  • Until they complete their childbearing
• Age‐related risk, however, differs between BRCA1 and BRCA2 carriers:
  • BRCA1 carriers are at an elevated lifetime risk for ovarian cancer compared to BRCA2 carriers and are also more likely to develop it earlier in life:
    • Specifically, women with BRCA1 mutations have an:
      • Average age at ovarian cancer diagnosis of 50 years
      • A significantly increased ovarian cancer risk starting at 35 years:
        • Which continues to increase with age
  • Women with BRCA2 mutations:
    • Have an average age of ovarian cancer diagnosis of 60 years
    • A significantly increased ovarian cancer risk starting at 50 years:
      • Which then plateaus at a 14% risk
    • Therefore, BRCA2 carriers may elect to defer RRBSO to a later age compared with BRCA1 carriers:
      • However, if they choose to do so, they must be counseled that they may not receive the benefit of decreased breast cancer risk after RRBSO
• Nevertheless, the society of Gynecologic Oncology (SGO):
  • Continues to recommend that BRCA1 and BRCA2 mutation carriers:
    • Undergo RRBSO after completing childbearing or by age 35 to 40 years
• Thorough preoperative counseling is critical in helping patients decide whether to proceed with RRBSO:
  • RRBSO is generally performed laparoscopically and is a low‐risk procedure:
    • The reported complication rate (both major and minor) of RRBSO:
      • Has been quoted as 4% but is even lower at high volume institutions
  • In addition, patients must be advised that there is a 4% to 8% risk of discovering an occult malignancyeither at the time of RRBSO or on final pathology
  • Preoperative serum CA125 should be obtained and patients should undergo a pelvic ultrasound
  • Patients should be consented for ovarian cancer staging surgery in case visible disease is seen and counseled that an occult malignancy may be detected on final pathology, thus requiring additional surgery
  • Women should also be counseled that at the time of RRBSO they will undergo surgical menopause and may begin to experience hot flashes, mood changes, vaginal dryness, dyspareunia, decreased libido, osteoporosis, cardiovascular disease, and possible impaired cognitive function:
    • Although surgical menopause before age 45:
      • Has been associated with increased overall mortality in the general population, this risk must be balanced with the substantially decreased all‐cause mortality after risk‐reducing surgery for the high‐risk HBOC population
    • Nonhormonal agents should be used as a first‐line therapy for these symptoms:
      • But hormonal replacement therapy (HRT) is also likely safe on the basis of a recent study of almost 900 postoophorectomy BRCA1 mutation carriers:
        • In that prospective longitudinal study, investigators found that HRT use was not associated with an increased risk of breast cancer (HR 0.97, 95% CI, 0.62‐1.52, P = .89)
        • However, when analyzing only women who used HRT:
          • The incidence of breast cancer was lower with estrogen‐only HRTcompared with combination estrogen and progesterone (12% vs 22%, log‐rank P = .04)
          • Estrogen‐only HRT is only recommended for women who have undergone a hysterectomy, as without progesterone support, it significantly increases the risk for endometrial cancer in the general population
        • A recent meta‐analysis including three trials with 1100 patients also demonstrated there was not a significantly higher breast cancer risk associated with HRT after RRBSO in BRCA1 and BRCA2 mutation carriers (HR 0.98, 95% CI, 0.63‐1.52)
        • Nevertheless, the relationship between HRT and individual all‐cancer risk is complex and imperfectly understood at this time
        • The results of long‐term, prospective studies are necessary to draw more definitive conclusions in this high‐risk population
• References:
  • Domchek SM, Friebel TM, Singer CF, et al. Association of risk‐ reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304(9):967‐975. 
  • Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophor- ectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346(21):1616‐1622. 
  • Kauff ND, Satagopan JM, Robson ME, et al. Risk‐reducing salpingo‐ oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346(21):1609‐1615. 
  • Antoniou A, Pharoah PDP, Narod S, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003;72(5):1117‐1130. 
  • Manchanda R, Abdelraheim, Johnson M, et al. Outcome of risk‐ reducing salpingo‐oophorectomy in BRCA carriers and women of unknown mutation status. BJOG. 2011;118(7):814‐824. 
  • Rocca WA, Grossardt BR, de Andrade M, Malkasian GD, Melton LJ. Survival patterns after oophorectomy in premenopausal women: a population‐based cohort study. Lancet Oncol. 2006;7(10):821‐828. 
  • Kotsopoulos J, Gronwald J, Karlan BY, et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncology. 2018;4(8):1059. 
  • Marchetti C, De Felice F, Boccia S, et al. Hormone replacement therapy after prophylactic risk‐reducing salpingo‐oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a meta‐ analysis. Crit Rev Oncol Hematol. 2018;132:111‐115. 

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