Breast cancer during pregnancy and pregnancy after treatment

1. Breast cancer during pregnancy and pregnancy after treatment Belgian Breast Meeting 13-10-2006 Frederic Amant Gynaecologic Oncology Multidisciplinary Breast Center Katholieke Universiteit Leuven

2. ‘To begin my life with the beginning of my life, I record that I was born’ Ch. Dickens in : The personal history of David Copperfield, 1850

3. Negative influence on human development Infections Teratogens Alcohol Cocaine Tobacco Nutritional deficiency Cytotoxic treatment????

4. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after breast cancer

5. Study center Perinatal Epidemiology (SPE)

7. Pathology It appears that the histopathologic and immunohistochemical findings of the tumors of pregnant women with BC are similar to those of non-pregnant young women with BC. It is more likely that age at diagnosis rather than the pregnancy determines the biologic features of the tumor.

8. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

9. Breast cancer surgery during pregnancy • Risk of abortion is highest before 12 weeks • Majority underwent mastectomy due to fear for radiotherapy • Breast conserving surgery with axillary LN dissection • Especially third trimester • Chemotherapy before radiation • Sentinel node: Tc • Gentilini et al., Ann Oncol 2004;15:1348-51 • Keleher et al., Breast J 2004;10:492-5

10. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

11. Radiotherapy, Kal, Lancet Oncol 2005 Breastca, supradiaphragmatic Hodgkin’ disease, Brain tumors, head– and necktumors Distance Shielding with lead protection < 0.01 Gy exposure Slight increase leukemia, tumors during childhood 0.003-0.004 (nl 0.002-0.003) • 0.2 Gy: effect dependent pregnancy duration • Multidisciplinary approach

12. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

13. Anthracyclins • Doxorubicin (Adriblastina°) • Epirubicin (Peccatori et al., Lancet Oncol 2004;5:398) • Slightly more lipophylic • Faster influx • Less intracellular retention • Shorter elimination half life • Better therapeutic index • Less systemic and cardial toxic effects • No fetal complications (n=14) • Idarubicin • More lipophylic • Higher affinity for DNA

14. Pharmacokinetics during pregnancy: preliminary data

15. Taxanes during pregnancy

16. Trastuzumab during pregnancy

17. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

18. Chemotherapy during 2nd and 3rd trimester:IUGR, premature birth, IUD, neonatal death • Pizzuto et al., Cancer Treat Rep 1980;64:679 • Mulvihill et al., Cancer 1987;60:1143 • Zemlickis et al., Arch Intern Med 1992;152:573 • Zemlickis et al., Am J Obstet Gynecol 1992;166:781 • Partridge & Garber, Sem Oncol 2000;27:712 • Hansen et al., Am J Obstet Gynecol 2001;97:809 • Peres et al., Braz J Med Biol Res 2001;34:1551 • Ali et al., Leuk Res 2003;27:381 Follow up in high-risk obstetrical unit to determine optimal moment of delivery

19. Chemotherapy during pregnancy: 1966-2004Cardonick & Iacobucci, Lancet Oncol 2004;5:283 • N = 376, mostly after organogenesis • 19 (5%) foeti and 1% neonati died • 16 in hematological malignancies • 2/3 received idarubicine for breastca • 28 (7%) IUGR, 18 (5%) premature birth • 15 (4%) neonatal transient myelosuppression • 9/11 malformations occurred after 1st trimester exposure

20. Avoidance of prematurityZhao et al., Int J Gynecol Cancer 2006;16:8-15 • Series of 22 cases of ovarian cancer during pregnancy • 14 deliveries • 1 neonatal death • C/S at 31 weeks • Died of respiratory distress syndrome

21. Fetal maturity

22. 18 year experience from 5 London teaching hospitalsRing et al., J Clin Oncol 2005;18:4192-7 • 28 women (24 curative, 4 palliative) • Chemotherapy: AC or EC (n=16) or CMF (n=12) • 1/28: 1e trim → miscarriage

23. Last chemo-delivery: > 3w interval • Maternal neutropenia and thrombocytopenia • Metabolisation in placenta (fœtus) versus inefficient neonatal liver and kidney function(neonate) • Neonatal myelosuppression • Okun et al., Med Ped Oncol 1979;7:315 • Pizzuto et al., Cancer Treat Rep 1980;64:679 • Reynoso et al., JCO 1987;5:1098 • Raffles et al., Br J Obstet Gynaecol 1989;96:1099 • Avilés et al., Am J Hematol 1991;36:243 • Garcia et al., J Perinatol 1999;19:230

24. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

25. Long term outcomes: retrospective dataAvilés and Neri, Clinical Lymphoma 2001;2:173-7 • Update on Aviles et al., Am J Hemat 1991;36:243-8 • 84 children • Hematological malignancies (29 malignant lymphoma, 26 Hodgkin, 29 acute leukemia) • 38 received chemotherapy during 1st trimester • 19 y follow up (range, 6-29 years) • Normal fysical, neurological, psychological, hematological and immunological function

26. MD Anderson dataHahn et al., Cancer 2006 • N = 57 (32 adj CT, 25 NACT), FAC • Survey: mail or telephone • Children age (n=40): 2-157 mts

27. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

28. Methods • Retrospective search of cases • Prospective • Standardised clinical neurologic assessment • Echocardiografy with dopplers

29. Results: maternal data (last FU, 9-2006)

30. Results: neonatal and pediatric follow-up (last FU, 9-2006)

31. Standard echocardiographic data Van Calsteren et al., J Clin Oncol 2006;24(12):e16-7

32. Breast cancer during pregnancy Surgery Radiotherapy Chemotherapy Farmacology Short term neonatal outcome Long term pediatric outcome Prospective data Pregnancy after treatment

33. Pregnancy after treatment • No difference in survival • ‘Two year cancer diagnosis anniversary’ • Higher rate of miscarriages • Individual’s response to therapy • Receptor positive: • Tamoxifen contraindicated (ambiguous genitalia, Goldenhar syndrome) • After completion hormonal treatment

34. Breast cancer during pregnancy and pregnancy after treatment : conclusions • Radiotherapy is possible • Chemotherapy • Short term (neonatal) safety evidence • Long term outcome: retrospective data suggest safety • Prospective trials needed • Larger numbers • Longer follow up • Thorough assessment • Morbidity related to –induced- prematurity

35. ¡¡¡ Thank you!!!