Gender and Cancer Does the disease occur more frequently in one sex vs. the other? Diagnostic bias? Due to exposure? Due to genetic predisposition? Does the disease behave differently in one sex vs the other? Modulated hormones? Gender-based lifestyle differences? Interactions that we don’t understand? Are there different consequences to the disease or treatment that depend on gender?
Sex Ratio Hematologic diseases DiseaseMale:Female Ratio AML1:1 ALL1.3:1.0 HD1.3:1.0 Multiple Myeloma1.4:1 CLL2:1 CML3:2 ETFemale Predominance PV1.2:1.0 MF1:1
Cartwright et al. British Journal of Hematology 2002, 118 1071-1077 More women diagnosed than men More men diagnosed than women
Clinical Trial Inclusion Trial Total Patients MaleFemale HU in High-Risk ET NEJM 1995 11437 (32%)77 (68%) ASA in PV NEJM 2004 518 308 (59%) 210 (41%) HU vs Anagrilide in high-risk ET NEJM 2005 809 342 (42%) 467 (58%) Ruxolitinib in MF (US Study) NEJM 2012 309 167 (54%) 142 (46%)
Topics to Discuss Overview: Gender and Cancer Gender and MPNs Special issues facing females with MPNs Clotting Pregnancy Bleeding Modifiable risk factors – both genders Conclusions
Challenges: Clotting ET – most common MPN in fertile women Hormonal contraception + ET = hypercoaguable state Pregnancy + ET = hypercoaguable state Thrombosis -- #1 cause of maternal death
Challenges: Fertility Contraception Combination hormones >progesterone only OCPs General population have a 3–6- fold increased risk of venous thrombosis with OCPs One retrospective study of >300 patients. Subset on OCPs ET + OCPs = 23% VTE ET no OCPs = 7% VTE
Challenges: Pregnancy Pregnancy outcomes likely impacted Live birth rate 50-70% First trimester loss 10-20% Late pregnancy loss 10% Increased rates of placental abruption, intrauterine growth restriction Can we change those outcomes?
Preconception Counseling Risk Assessment Prior VTE or arterial clot Prior hemorrhage Prior pregnancy complication Diabetes or Hypertension requiring treatment Platelet count of >1500 X 10 9 before or during pregnancy
Preconception Counseling Multidisciplinary approach Discussion of teratogenic drugs Therapeutic options Aspirin LMWH Cytoreductive therapy Delivery and post-partum plan Breastfeeding information
Pregnancy: Low-Risk Patients Generally Continue low-dose aspirin Monitor platelet or Hct Keep HCT under 45% Consider venesection if necessary Increased plasma volume of pregnancy means no set targets Antiplatelet agents reduce risk of VTE in ET patients Pregnancy is thrombotic Aspirin is likely safe in pregnancy (APLA pts)
Pregnancy: High-risk patients Remove possible teratogeneic drugs Taper off hydrea or anagrilide 3-6 months prior to conception Hydrea likely contraindicated, men and women Anagrilide crosses the placenta Cytoreduction Interferon-alpha -- Case reports indicating likely safe Prevent Clotting LMWH Prophylactic or, in some cases, therapeutic doses
Challenges: Bleeding More common when platelets are elevated 1,000-1,500 X 10 9 Often related to acquired Von Willebrands Disease Occurs in both men And women
Topics to Discuss Overview: Gender and Cancer Gender and MPNs Special issues facing females with MPNs Pregnancy Clotting Bleeding Modifiable risk factors – both genders Conclusions
Outcomes: Venous, Arterial Events like stroke, heart attack, VTE, bleeding MPN Smoking lipids Exercise Healthy Weight DM HTN control
Conclusions Get involved in your care Ask questions Participate in clinical trials Control what you can Any questions?