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Matteo Lambertini, MD ESMO Fellow Institut Jules Bordet, Brussels (Belgium) Physicians Attitudes and Knowledge about Fertility Preservation Lugano, Switzerland October 7, 2018 Do not duplicate or distribute without permission from author and ESO

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Matteo Lambertini, MDESMO Fellow

Institut Jules Bordet, Brussels (Belgium)

Physicians Attitudes and Knowledge about Fertility Preservation

Lugano, SwitzerlandOctober 7, 2018Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Disclosure InformationRelationship Relevant to this Session

Lambertini, Matteo:

• Consultant or advisor: Teva

• Honoraria: Theramex

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istribute without

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ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

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istribute without

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ion from author a

nd ESO

“Fertility and pregnancy-related issues are one of the five priority areas of concern for

young women with breast cancer”

Fertility and Pregnancy-related Issues: Young Women Advocates Statement

Paluch-Shimon S et al, Breast 2017;35:203-17

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Peccatori F et al, Ann Oncol 2013;24:vi160-70. Oktay K et al, J Clin Oncol 2018;36(19):1994-2001

ESMO GUIDELINES 2013

ASCO GUIDELINES 2018

Oncofertility Counseling is Mandatory As soon as Possible after Diagnosis

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Lambertini M et al, Breast 2018;42:41-9

105 (45%) respondents

168 (7%) respondents

273 respondents

1

A BCY3/ BCC 2017 survey on physicians’ knowledge, attitudes and practice on fertility and pregnancy issues in young breast cancer patients

1) Demographic, medical training and background information (Q1-Q10)

Q1. Age

· _________ years

Q2. Gender

· Male

· Female

Q3. What is your country of practice?

· ____________________

Q4. What is your religion?

· Catholic

· Protestant (Anglican, Methodist etc)

· Muslim

· Hindu

· Jewish

· Atheist/none

· Other, please specify: ____________________

· I prefer to not answer

Q5. Do you have children or have currently parenthood project?

· Yes

· No

Q6. What is your speciality? (Please check all that apply)

· Medical oncology

· Radiation oncology

· Surgical oncology

· Other, please specify: ____________________

Q7. What is your clinical practice environment?

· Academic

· Private

· Both (academic and private)

· Other, please specify: ____________________

Q8. How many years of clinical practice (including your MD specialisation) do you have?

· _________ years

1

A BCY3/ BCC 2017 survey on physicians’ knowledge, attitudes and practice on fertility and pregnancy issues in young breast cancer patients

1) Demographic, medical training and background information (Q1-Q10)

Q1. Age

· _________ years

Q2. Gender

· Male

· Female

Q3. What is your country of practice?

· ____________________

Q4. What is your religion?

· Catholic

· Protestant (Anglican, Methodist etc)

· Muslim

· Hindu

· Jewish

· Atheist/none

· Other, please specify: ____________________

· I prefer to not answer

Q5. Do you have children or have currently parenthood project?

· Yes

· No

Q6. What is your speciality? (Please check all that apply)

· Medical oncology

· Radiation oncology

· Surgical oncology

· Other, please specify: ____________________

Q7. What is your clinical practice environment?

· Academic

· Private

· Both (academic and private)

· Other, please specify: ____________________

Q8. How many years of clinical practice (including your MD specialisation) do you have?

· _________ years

Physicians Attitudes and Knowledge about Fertility Preservation

Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Donnez J & Dolmans MM, N Engl J Med 2017;377(17):1657-65Peccatori F et al, Ann Oncol 2013;24:vi160-70. Oktay K et al, J Clin Oncol 2018;36(19):1994-2001

Embryo/Oocyte CryopreservationAvailable Guidelines

Guidelines Year Recommendations

ESMO 2013 Embryo or oocyte cryopreservation is the main method to preserve female fertility. Ovarian stimulation should be carried out before commencing chemotherapy.

ASCO 2018 Embryo cryopreservation is an established fertility preservation method, and it has routinely been used for storing surplus embryos after in vitro fertilization.Cryopreservation of unfertilized oocytes is an option, and may be especially well suited to women who do not have a male partner, do not wish to use donor sperm, or have religious or ethical objections to embryo freezing.Do not duplica

te or distr

ibute without

permiss

ion from author a

nd ESO

Embryo/Oocyte Cryopreservation

Prescription

Knowledge

Availability

Lambertini M et al, Breast 2018;42:41-9

Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Embryo/Oocyte Cryopreservation: Efficacy Data

Oktay K et al, J Clin Oncol 2015;33(22):2424-9. Diaz-Garcia C et al, Fertil Steril 2018;109(3):478-85

Ooctye cryopreservationProspective multicenter cohort study

n=618 breast cancer patients

Embryo cryopreservation Prospective single-center cohort study

n=131 breast cancer patients

Pregnancy rate = 20/33 (61%) Pregnancy rate = 13/38 (34%)

33/131 (25%)

38/618 (6%)

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Controlled ovarian stimulation should be cosidered safe in all

patients

0%

20%

40%

60%

80%

100%

Disagree

Neutral

Agree

19% 24% 57%

Embryo/Oocyte Cryopreservation: Safety Concerns

Lambertini M et al, Breast 2018;42:41-9

Controlled ovarian stimulation should not be cosidered safe in patients:

• With hormone receptor-positive disease

• Candidates to neoadjuvant chemotherapy

22% of respondents agreed

18% of respondents agreed

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Embryo/Oocyte Cryopreservation: Safety Data

Kim J et al, J Clin Endocrinol Metab 2016;101(4):1364-71 Rodriguez-Wallberg KA et al, Breast Cancer Res Treat 2018;167(3):761-9. Moravek MB et al, Fertil Steril 2018;109(2):349-55

MortalityRecurrence

Retrospective single-center cohort study

n=114 FP & n=148 no FP

Retrospective cohort study (Swedish registry)

n=188 FP & n=378 no FP

Relapse-free survival

Prospective single-center cohort study

n=120 FP & n=217 no FP

Relapse-free survival

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Embryo/Oocyte Cryopreservation: Safety Data

Hormone-receptor status Timing of chemotherapy administration

Kim J et al, J Clin Endocrinol Metab 2016;101(4):1364-71. Meirow D et al, Fertil Steril 2014;102(2):488-95. Oktay K et al, J Clin Oncol 2015;33(22):2424-9. Letourneau JM et al, Hum Reprod 2017;32(10):2123-9. Chien AJ et al, BCRT 2017;165(1):151-9

Do not duplicate or d

istribute without

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ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

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istribute without

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ion from author a

nd ESO

Ovarian Tissue CryopreservationUpdated Guidelines

Guidelines Year Recommendations

ESMO 2013 Ovarian tissue cryopreservation is still considered experimental, but remains a unique option for young girls with cancer

ASCO 2018 Ovarian tissue cryopreservation remains experimental. However, emerging data may prompt reconsideration of this designation in the future (this technique is already considered non-experimental in some countries, and its experimental status is undergoing evaluation in the United States)

Donnez J & Dolmans MM, N Engl J Med 2017;377(17):1657-65Peccatori F et al, Ann Oncol 2013;24:vi160-70. Oktay K et al, J Clin Oncol 2018;36(19):1994-2001

Do not duplicate or d

istribute without

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ion from author a

nd ESO

Ovarian Tissue Cryopreservation

Prescription

Knowledge

Availability

Lambertini M et al, Breast 2018;42:41-9

Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Ovarian Tissue CryopreservationEfficacy Data

Fleury A et al, J Gynecol Obstet Hum Reprod 2018; [Epub ahead of print]. Diaz-Garcia C et al, Fertil Steril 2018;109(3):478-85

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Ovarian Tissue CryopreservationSafety Data

Fleury A et al, J Gynecol Obstet Hum Reprod 2018; [Epub ahead of print]

Risk of malignant contamination appears to be low in breast cancer patients

Do not duplicate or d

istribute without

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ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

Do not duplicate or d

istribute without

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ion from author a

nd ESO

Ovarian Suppression with GnRHa during CTUpdated Guidelines

Paluch-Shimon S et al, Breast 2017;35:203-17. Lambertini M et al, Eur J Cancer 2017;71:25-33Oktay K et al, J Clin Oncol 2018;36(19):1994-2001

Guidelines Year Recommendations

ESO-ESMO BCY3 2017 GnRHa should be discussed as an option with all patients interested in potentially preserving fertility and/or ovarian function who are candidates for chemotherapy, irrespective of tumor subtype

AIOM 2017 GnRHa during chemotherapy should be recommended to all pre-menopausal breast cancer patients undergoing chemotherapy who are interested in ovarian function and/or fertility preservation

ASCO 2018 When proven fertility preservation methods are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. GnRHa should not be used in place of proven fertility preservation methods.

Updated ESMO and ESHRE guidelines are upcoming

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Ovarian Suppression with GnRHa during CT

Prescription

Knowledge

Availability

Lambertini M et al, Breast 2018;42:41-9

Do not duplicate or d

istribute without

permiss

ion from author a

nd ESO

Ovarian Suppression with GnRHa during CTEfficacy Data

Lambertini M et al, J Clin Oncol 2018;36(19):1981-90

Premature Ovarian Insufficiency (POI)

Post-Treatment Pregnancies

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Ovarian Suppression with GnRHa during CTSafety Data

Lambertini M et al, J Clin Oncol 2018;36(19):1981-90

ER+

ER-

Disease-Free Survival Overall Survival

HR 1.17; 95% CI 0.62-2.20 HR 0.79; 95% CI 0.24-2.59

HR 0.95; 95% CI 0.64-1.42 HR 0.65; 95% CI 0.39-1.07

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istribute without

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ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

Do not duplicate or d

istribute without

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ion from author a

nd ESO

Physicians Attitudes and Knowledge about Fertility Preservation in Advanced Breast Cancer

How often do you discuss the possible treatment-related loss of ovarian function and fertility in young breast cancer patients before starting anticancer therapies ?

Courtesy of S. Paluch-Shimon

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Physicians Attitudes and Knowledge about Fertility Preservation in Advanced Breast Cancer

Courtesy of S. Paluch-Shimon

I feel it irresponsible towards future children who may end-up orphaned from their mother

45%

Future pregnancy is not safe in this clinical setting 42%

Fertility preservation and future pregnancy in this clinical setting is irrelevant therefore I have no obligation to discuss this with the patient

18%

Fertility preservation is not safe in this clinical setting 17%

Reasons for NOT discussing fertility preservation with women with ABC?

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Fertility Preservation in Advanced Breast CancerCurrent Recent Guidelines

Cardoso F et al, Ann Oncol 2018;29(8):1634-57

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ion from author a

nd ESO

Outline• Introduction

• Attitudes and knowledge about:

– Embryo/oocyte cryopreservation

– Cryopreservation of ovarian tissue

– Temporary ovarian suppression with GnRHa duringchemotherapy

• Attitudes and knowledge about fertility preservation in advanced breast cancer

• Conclusions

Do not duplicate or d

istribute without

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ion from author a

nd ESO

• Fertility preservation and pregnancy-related issues are priority areas of concern for young breast cancer patients

• As early as possible after diagnosis, a proper oncofertility counseling is mandatory to inform all women irrespectively of the stage of their disease

• Embryo/oocyte cryopreservation are standard options for fertility preservation

• Ovarian tissue cryopreservation remains experimental in most of the countries but may be discussed in specific circumstances

• Temporary ovarian suppression with GnRHa during chemotherapy should now be considered an available option to preserve ovarian function and potential fertility in young breast cancer patients (but not an alternative to cryopreservation techniques)

• Improving physicians awareness and education in this field is crucial as well as strengthening the collaboration between oncologists and fertility specialists

Conclusions

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Institut Jules BordetAhmad AwadaMartine PiccartChristos SotiriouFrederic HenotBastien NguyenGiulia Viglietti

Evandro de AzambujaMichail IgnatiadisNoam F. PondeSamuel MartelChristian MaurerFrancois Richard

San Martino – IST HospitalLucia Del MastroFrancesca PoggioAlessia Levaggi

Paola AnseriniMaria Carolina PescioChiara Dellepiane

Istituto Europeo di OncologiaFedro A. Peccatori

American University of BeirutHatem A. Azim Jr.

Dana-Farber Cancer Institute

[email protected]

@matteolambe

Erasme HospitalIsabelle DemeestereFlorence Horicks

Oranite GoldratMargherita Condorelli

Breast International GroupDebora Fumagalli

Ann H. Partridge Philip Poorvu

Zambrano Hellion HospitalCynthia Villarreal-Garza

Shaare Zedek Medical CentreShani Paluch-Shimon

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