Contraception after ovarian and breast cancers final · 5/12/2018 · Conclusions on ovarian cancer In patients with conservative treatment, COC or progestin can be used but if we

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BUDAPEST, HUNGARY, 9 -12 MAY 2018

Hormonal contraception after breast cancer and ovarian

cancer

BUDAPEST, HUNGARY, 9 - 12 MAY 2018

Pr . Anne Gompel, U n ité G y n é c o lo g ie E n d o c r in ie n n e ,

C o c h in - P o r t R o y a lP a r is

anne.gom pel@ parisdescartes.fr


COI

• M e m b e r o f a n a d v is o r y b o a r d M IT H R A ( E s t e t r o l in M e n o p a u s e )

• P a r t ic ip a t io n w it h o u t h o n o r a r iu m t o s y m p o s ia o r g a n is e d b y B e s in s , M y la n

• in d ir e c t

– M e m b e r o f th e b o a rd E S C– E x m e m b e r o f E M A S a n d IM S b o a rd s

– M e m b e r o f G E M V I b o a rd


Breast Cancers /age

20-25% of breast cancers before 50 years


Contraception is indicated

• To program pregnancy• Amenorrhea is frequently occurring after a chemotherapy +

Tamoxifen ≠infertility• No predictive value of hormone tests• Climacteric symptoms?


Gonadal toxicity• Depends on the age+++

• Mild if <35 years• High if >45 years• The most the amenorrhea lasts the more risk of being definitive

(Sukumvanich P, et al., Cancer 2010)

• On the ovarian reserve

• On chemotherapy: nature and dose


To x ic i té g o n a d iq u e d e s a g e n ts c y to to x iq u e s (WallaceWHetal,LancetOncol,2005)

+ ta x a n s (Tham YL et al Am J Clin Oncol. 2007;30:126–32. Long JP,Eur Rev

Med Pharmacol Sci. 2016;20:1087-92.)

Toxicity of chemotherapy(Wallace et al Lancet Oncology 2005)

High intermediate low risk

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Breast Cancer and contraception at Basel

• Basel Register of breast cancer 1990 to 2007• 100 women had a BC before 40 years • Which contraception 1 year after the diagnostic?- 42 did not need a contraception- 4 copper IUD - 52 were using a contraception with low reliability• 90% of oncologists ask the question when starting the

treatment and only 30% further on (U. Güth et al The Breast 30 (2016) 217e221)

(Guth et al, Eur J Contracept Reprod Health Care.2016;21:290-4)


In France(Hamy AS, et al Eur J Gynaecol Oncol. 2014;35:149-53.)

• Survey among gynecologists197 answers

• 73.1% copper IUD• 21.3% hormonal contraception• condoms n=14, definitive contraception n = 7, others n = 8


OMS recommendations 2010

• No hormonal contraception during the treatment of a BC

• Non hormonal contraception are recommended especially copper IUD

• after 5 years: an hormonal contraception has to be avoided if possible but if there is no other solution can be discussed any hormonal contraception


Horm onal Contraception and cancer HR - ? (Rosenberg L et al, Cancer Epidem iol Bio Prev 2010)

53,848 Black Women's Health Study participants from 1995–2007 through biennial health questionnairesEver use : 279 cases, RR=1,65 (1,19-2,30) cancers ER- PR-

Same contrindications


Is there a place for LNG-IUD?• In a low power study (Trinh BX et al, Fertil Steril, 2008) more recurrence if LNG-

IUD in place at the diagnosis HR=3.39(1.01-11.35) but not if inserted after HR=1.48 (0.62-3.49)• RR of BC in LNG-IUD users

– S t u d y f r o m r e g i s t e r s (Lyytinen et al., Int J Cancer 2010) H R = 1 . 4 5 ( 1 . 9 7 - 1 . 7 7 )

• Idem (Soini T, Obstet gynecol 2014 – Acta Oncologica 2016) S I R = 1 . 1 9 ( 1 . 1 3 - 1 . 2 5 ) > 5 y e a r s , 2

i n s e r t i o n s C L I : S I R = 1 . 7 3 ( 1 . 3 7 – 2 . 1 5 ) ; C C I : S I R = 1 . 3 7 ( 1 . 2 1 – 1 . 5 3 ) • D a n i s h r e g i s t e r s H R = 1 . 2 1 ( 1 . 1 1 - 1 . 3 3 ) (Morch LS et al, N Engl J Med. 2017)

• N o r w e g i a n W o m e n a n d C a n c e r S t u d y , 1 0 4 , 3 1 8 w o m e n , 9 , 1 4 4 e v e r u s e r s a n d 9 5 , 1 7 4 n e v e r u s e r s o f L N G - I U S . R R = 1 . 0 3 ( 0 . 9 1 - 1 . 1 7 ) I F > 5 y e a r s o f u s e R R

= 0 . 8 8 ( 0 . 6 8 - 1 . 1 6 ) (Ja re id M e t a l, G y n e co l o n co l, 2 0 1 8 )


Cochrane «Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen »

• 4 RCT- 543 pre and post-menopausal women (71%) receiving tamoxifen• 273 treated, 270 controls

N studiesPolyps 2

412 mois : OR=0,22 (0,08-0,64)

24-60 mois : OR=0,22 (0,13-0,39)

Hyperplasia 4 (0 cas vs 6 cas) : OR=0,13 (0,03-0,67)Cancer 4 0 cas

Myomes 3 N=13, OR = 0,48 (0,16–1,46)Saignements

anormaux421

12 mois : OR 7.26, CI 3.37–15.6624 mois : OR 2.72, CI 1.04–7.10

45-60 mois : 0 cas

B r e a s t c a n c e r R e c u r r e n c e 1 1 c a s e s 7 c o n t r o ls

D e a t h s 8 c a s e s 8 c o n t r o ls

(Dominick S et al , 2015)

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Conclusions

• BC is an hormone dependent cancer• Providing an efficient contraception is mandatory

• Hormonal contraception is not recommended • A discussion for use of LNG-IUD is possible in case of

gynecological indications

• Scarce data are available on the risk of recurrence with this IUD


OVARIAN CANCER

3 0 .6 %


Horm onal contraception decreases the risk of ovarian cancer and borderline tum ors

• All the studies with COC show a decrease in the RR of invasive epithelial carcinoma except the mucinous differentiation

• Few have looked at the borderline tumors and found the same trend of decrease

• LNG-IUD decreases the RR of ovarian cancer (Soini et al Acta Oncologica

2016, Jareid M et al, Gynecol oncol, 2018)


W hich cancer could be concerned by a contraception?

• high grade serous tumors, endometrioid, mucinous carcinoma, low-grade serous, clear cell carcinoma are usually treated by ovariectomy, debulking, chemotherapy

• Borderline tumors• Malignant Ovarian Germ Cell TumorsImmature teratoma• Sex Cord-Stromal TumorsGranulosa cell tumor, Sertoli-Leydig cell tumor


Recom m endations for contraception by a panel of French experts

(Rousset-Jablonski C et al, Bull Cancer, 2018)

• D u r in g c h e m o t h e r a p y t h e in c r e a s e d r is k o f V T E C I C O C b u t n o n h o r m o n a l c o n t r a c e p t io n , p r o g e s t in s o r G n R H a n a lo g u e s c a n b e u s e d

• H o r m o n a l c o n t r a c e p t io n a r e n o t c o n t r a in d ic a t e d in w o m e n t r e a t e d fo r b o r d e r l in e t u m o r s , g e r m c e l l c a r c in o m a , im m a t u r e t e r a t o m a a f t e r t h e e n d o f t h e

t r e a t m e n t p e r io d ( b u t d a t a a r e la c k in g )• A f t e r a c o n s e r v a t iv e t r e a t m e n t fo r h ig h g r a d e t u m o r s h o r m o n a l c o n t r a c e p t io n

a r e n o t C I• In c a s e o f c o n s e r v a t iv e t r e a t m e n t in lo w s e r o u s g r a d e t u m o r s h o r m o n e s a r e C I

• In c a s e o f g r a n u lo s a c e l l t u m o r s :

– h ig h d o se p ro ge stin is re co m m e n d e d ( d ata w ith h ig h d o se s p ro ge stin s) – B e ca u se o f a se n s it izatio n b y e stro ge n s o f FS H re ce p to rs to FS H , e stro ge n s a re n o t

re co m m e n d e d . (a ro m ata se in h ib ito rs a re u se d in inva s ive ca se s… )

– S a m e w ith Le yd ig ce ll tu m o rs?BUDAPEST, HUNGARY, 9 -12 MAY 2018

Granulosa cell tum ors and antigonadotropic/progestin treatm ent

Hardy RD Gynecol oncol 2005

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Conclusions on ovarian cancer

In patients with conservative treatment, COC or progestin can be used but if

we have a lot of data on the protective effect of COC and the ovarian cancer, there is a lack of data after treatment of an ovarian cancer.

Attitudes have recently been challenged in particular in borderline tumors.

We thus have to manage more patients with potential fertility for whom

contraception is necessary.

More information are needed for rare ovarian tumors and the impact of hormones

Granulosa cell tumors are considered as a CI to estrogens as well as low grade

serous tumors to hormones

The other types may receive COC or progestin contraceptives

Documents

Contraception after ovarian and breast cancers final · 5/12/2018 · Conclusions on ovarian cancer In patients with conservative treatment, COC or progestin can be used but if we