1.
Dr. Francisco Quereda y Dr. Gabriel Fiol
TRATAMIENTO DE LA AVV EN
SUPERVIVIENTES DE CÁNCER DE MAMA
Profesor Titular / Jefe de Servicio de
Ginecología
Universidad Miguel Hernández /
Hospital Universitario de San Juan de
Alicante
Ginecólogo Adjunto /
Hospital Universitario Torrecardenas de
Almeria / Alborán, Centro Médico de la
Mujer

2.
ESTA PRESENTACIÓN TIENE UN OBJETIVO EXCLUSIVAMENTE INFORMATIVO Y HA SIDO CONCEBIDO COMO UN
SERVICIO A LA PROFESIÓN MÉDICA. SU CONTENIDO REFLEJA ÚNICA Y EXCLUSIVAMENTE LAS OPINIONES,
CRITERIOS, CONCLUSIONES Y/O HALLAZGOS PROPIOS DE SU AUTOR O AUTORES, QUE PUEDEN NO COINCIDIR
NECESARIAMENTE CON LA OPINIÓN DE LOS LABORATORIOS PROPIETARIOS/COMERCIALIZADORES DE LAS
MOLÉCULAS/MEDICAMENTOS MENCIONADAS EN LA PRESENTACIÓN. SE HA SOLICITADO A SU AUTOR QUE EL
CONTENIDO DE LA PRESENTACIÓN SEA EN SU TOTALIDAD VERAZ, PRECISO, EQUILIBRADO, LO SUFICIENTEMENTE
COMPLETO, Y NO ENGAÑOSO, Y QUE SE BASE EN TODO MOMENTO EN LA LITERATURA Y DATOS CIENTÍFICOS
RELEVANTES.
LA INFORMACIÓN PRESENTADA EN LA MISMA ES ACORDE EN SU TOTALIDAD CON LAS FICHAS TÉCNICAS
AUTORIZADAS POR LAS AUTORIDADES SANITARIAS COMPETENTES PARA LOS FÁRMACOS QUE SE MENCIONAN EN
LA MISMA.
ESTA PRESENTACIÓN ES PARA USO Y DIFUSIÓN EXCLUSIVOS EN EL PRESENTE EVENTO, POR LO QUE SE HA
SOLICITADO A SU AUTOR QUE NO REPRODUZCA SU CONTENIDO EN CONTEXTOS DIFERENTES AL DEL PRESENTE
EVENTO, Y, EN PARTICULAR, EN DECLARACIONES ANTE LOS MEDIOS DE COMUNICACIÓN O EN LAS REDES
SOCIALES. SE SOLICITA A LOS ASISTENTES, ASIMISMO, QUE NO PROCEDAN A REPRODUCIR EL CONTENIDO DE LA
PRESENTACIÓN DE FORMA ÍNTEGRA O PARCIAL.
EL PONENTE DECLARA QUE HA RECIBIDO HONORARIOS DE SHIONOGI, DE ACUERDO CON EL VALOR DE MERCADO
DE ESTE TIPO DE SERVICIOS, PARA LA PREPARACIÓN Y REALIZACIÓN DE LA PRESENTACIÓN.

3.
El cáncer de mama
Problema relevante y frecuente
- 24-26.000 nuevos casos de cáncer de mama y
- 6.000-6.300 fallecimientos (España INE).
- Incidencia en aumento.
- El 29% de cánceres de la mujer
- 18% de las muertes por cáncer (7.000/año, edad media 66)
- 1/3 de ellas antes de los 50 años
- Supervivencia media 15 años.
- Aproximadamente 350.000 mujeres en España (1/10-12 mujeres
climatéricas).
PSICOONCOLOGÍA. Vol. 4, Núm. 2-3, 2007, pp. 231-248 Correspondencia: Marina Pollán Santamaría Área de Epidemiología Ambiental y
Cáncer. Centro Nacional de Epidemiología. Instituto de Salud Carlos III. C/Sinesio Delgado, 6. 28029 Madrid. E-mail: mpollan@isciii.es
SITUACIÓN EPIDEMIOLÓGICA DEL CÁNCER DE MAMA EN ESPAÑA Marina Pollán

4.
El cáncer de mama
Cancer Survival and Incidence from the Surveillance, Epidemiology, and End Results (SEER) Program Lynn A. Gloeckler Ries, doi: 10.1634/theoncologist.8-6-541
The Oncologist December 2003 vol. 8 no. 6 541-552

5.
Cancer Survival and Incidence from the Surveillance, Epidemiology, and End Results (SEER) Program Lynn A. Gloeckler Ries, doi: 10.1634/theoncologist.8-6-541
The Oncologist December 2003 vol. 8 no. 6 541-552
SEER cancer statistics review, 1975-2005 Author(s) Ries, LAG; Year 2008 Publisher U.S. National Institutes of Health, National Cancer Institute Location
Bethesda, MD Number of Page 907 http://seer.cancer.gov/csr/1975_2005

6.
Impact of age, intrinsic subtype and local treatment on long-term local-regional recurrence and breast cancer mortality among low-risk breast cancer patients. Laurberg et al. Acta Oncol. 2017 Jan;56(1):59-67. doi:
10.1080/0284186X.2016.1246803. Epub 2016 Nov 16

7.
- Percepción de riesgo vital
- Cambio de imagen corporal y autoestima
- Efectos indeseables y adversos del tratamiento
adyuvante
- Menopausia precoz o temprana
- Impacto en sexualidad

8.
Atención a la mujer tras cáncer de mama: Objetivos
- Detección precoz de recidiva
- Prevención y/o diagnóstico de nuevos
tumores
- Evaluación y prevención del riesgo óseo
- Atención a síntomas climatéricos y
problemas de calidad de vida

9.
Perfil general de la atención al climaterio de la
mujer con cáncer de mama
- Necesidades de
cualquier mujer
- Necesidades
específicas
- Limitaciones para
su manejo

10.
Atrofia vulvovaginal
Johnston, S. (2002) The Recognition and Management of Atrophic Vaginitis. Geriatrics/Aging, 5, 9-15.

11.
Repercusiones genitourinarias de la menopausia
Sintomatología vaginal Sensación de sequedad
Prurito
Dispareunia
Coitorragia ocasional
Sintomatología urinaria Nicturia
Urgencia miccional
Disuria
Infecciones recidivantes
Disfunción sexual Reducción del deseo sexual
Evitación de actividad
Portman DJ, Gass ML; Vulvovaginal Atrophy Terminology Consensus Conference Panel. Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women's Sexual Health and the North American
Menopause Society. Menopause. 2014 Oct;21(10):1063-8. doi: 10.1097/GME.0000000000000329

12.
Impacto de la AVV en la sexualidad (FSFI).
EVES cohorte española
Palacios S, González SP, Fernández-Abellán M, et al.
Impact of Vulvovaginal Atrophy of Menopause in Spanish Women:
Prevalence and Symptoms According to the EVES Study.
Sex Med 2019 Jun; 7(2): 207–216.

13.
Aspectos de la vida de la mujer interferidos por la AVV.
S. Palacios, et al. (2017): Vulvar and vaginal atrophy as viewed by the
Spanish REVIVE participants: symptoms, management and treatment
perceptions. Climacteric. 2017;20:55-61.
S. Palacios, M. J. Cancelo, C. Castelo Branco, P. Llaneza, F. Molero & R. Sanchez Borrego (2017): Vulvar and vaginal atrophy as
viewed by the Spanish REVIVE participants: symptoms, management and treatment perceptions. Climacteric. 2017;20:55-61.

14.
Impacto de la AVV y patologías relevantes en la CV
Depresión
Fibromialgia
Dolor
Artritis
SVM moderados/severos
AVV moderada/severa
EPOC
Asma
Vejiga hiperactiva
Migraña
Angina
S. intestino irritable
Condiciones
con peor
calidad de vida
Scores EQ-5D de calidad de vida
DiBonaventura M. Journal of womens health. 2015;24:713-72. The association between vulvovaginal atrophy symptoms and quality
of life among postmenopausal women in the united states and western europe. DOI 10.1089/jwh.2014.5177 Vol 24 N 9, 2015

15.
Montazeri A et al, J Exp Clin Cancer Res 2008 Quality of life in patients with breast cancer before and after diagnosis: an eighteen months follow-up study BMC Cancer volume 8, Article number: 330
Revisiones sistemáticas sobre CV en pacientes con cáncer de mama
Autores Año Objetivo principal Conclusiones
- Existe repercusión negativa en diferentes áreas de la CV, por
el tratamiento quirúrgico y tratamientos adyuvantes
- La mayoría se normalizan después del tratamiento adyuvante
- No se identifican efectos negativos a largo plazo excepto por
los síntomas vasomotores y disfunción sexual

16.
Requisitos que un tratamiento para la AVV debe cumplir
Síndrome genitourinario de la menopausia: recomendaciones de la Sociedad Española de Ginecología y Obstetricia Genitourinary syndrome of menopause: Recommendations from the
Spanish Society of Obstetrics and Gynecology Santiago Palacios, Mª Jesús Cancelo Hidalgo. Prog Obstet Ginecol 2019;62(2):141-148

17.
¿Qué podemos hacer con la atrofia vulvovaginal de
estas mujeres y su síndrome genitourinario
relacionado?

18.
Article
AtrophicVaginitisin Breast Cancer Survivors: A Difficult
Survivorship Issue
JoanneLester 1,2,3,
*, Gaurav Pahouja 4
, Barbara Andersen 2,3
and Maryam Lustberg3,5,6
1
Clinical Research Nurse Practitioner, Division of Surgical Oncology, The Ohio State University,
Columbus, OH 43210, USA
2
Department of Psychology, The Ohio State University, Columbus, OH 43210, USA;
E-Mail: andersen.1@osu.edu
3
Comprehensive Cancer Center, Arthur G. James Comprehensive Cancer Hospital and Richard J.
Solove Research Institute, Columbus, OH 43210, USA; E-Mail: Maryam.lustberg@osumc.edu
4
Northeast Ohio Medical University, Rootstown, OH 44272, USA; E-Mail: gpahouja@kent.edu
5
Division of Medical Oncology, The Ohio State University, Columbus, OH 43210, USA
6
Stefanie Spielman Comprehensive Breast Center, 1145 Olentangy River Rd, Columbus,
OH 43212, USA
* Author to whom correspondence should be addressed; E-Mail: joanne.lester@osumc.edu;
Tel.: +1-614-519-8995.
Academic Editor: Jane Armer
Received: 21 January 2015 / Accepted: 13 March 2015 / Published: 25 March 2015
Abstract: Management of breast cancer includes systematic therapies including chemotherapy
and endocrine therapy can lead to a variety of symptoms that can impair the quality of life
of many breast cancer survivors. Atrophic vaginitis, caused by decreased levels of
circulating estrogen to urinary and vaginal receptors, is commonly experienced by this
group. Chemotherapy induced ovarian failure and endocrine therapies including aromatase
inhibitors and selective estrogen receptor modulators can trigger the onset of atrophic vaginitis
or exacerbate existing symptoms. Symptoms of atrophic vaginitis include vaginal dryness,
- Modificaciones del estilo de vida
- Hidratantes vaginales
- Lubricantes vaginales
- Láser.
Terapia estrogénica
- Estrógenos sistémicos
- Estrógenos locales
- Otros: prasterona
- Ospemifeno
J Pers Med. 2015 Mar 25;5(2):50-66. doi: 10.3390/jpm5020050. Atrophic vaginitis in breast cancer survivors: a difficult survivorship issue. Lester J

19.
Eur Rev Med Pharmacol Sci. 2016 Oct;20(20):4190-4195.
Postmenopausal vulvovaginal atrophy (VVA) is positively improved by topical hyaluronic acid application. A prospective, observational study. Origoni M1
Int J Community Based Nurs Midwifery. 2016 Jan;4(1):69-78.
Comparison of the Hyaluronic Acid Vaginal Cream and Conjugated Estrogen Used in Treatment of Vaginal Atrophy of Menopause Women: A Randomized Controlled Clinical Trial. Jokar A

20.
© 2017Arroyo.ThisworkispublishedandlicensedbyDoveMedical PressLimited. Thefull termsof thislicenseareavailableat https://www.dovepress.com/terms.php
International Journal of Women’s Health 2017:9 591–595
International Journal of W omen’sHealth Dovepress
submit your manuscript | www.dovepress.com
Dovepress
591
O R I G I N A L R E S E A R C H
open access to scientifi c and medical research
Open Access Full Text Article
Fractional CO2
laser treatment for vulvovaginal
atrophy symptoms and vaginal rejuvenation in
perimenopausal women
César Arroyo
HM Montepríncipe University
Hospital Laser Unit, Madrid, Spain
Background:This study investigated a novel fractional carbon dioxide (CO2
) laser for treatment
of symptoms associated with vulvovaginal atrophy (VVA) in perimenopausal women.
Methods: The study included 21 perimenopausal women (mean age 45 7 years) treated three
times by CO2
laser resurfacing and coagulation of the vaginal canal tissue and mucosal tissue of
the introitus. Vaginal health index (VHI) scores were computed by the investigator at baseline
and follow-ups. Subjects reported on sexual function, satisfaction, and improvement with treat-
ment. A visual analog scale was used to measure discomfort with treatment.
Results:Vaginal health and subject assessment of vaginal symptoms improved with successive
treatments. At 12 weeks following the third treatment, 82% of the patients showed a statistically
significant improvement in VHI (P 0.05). Additionally, 81% of subjects reported improve-
ment in sexual gratification, 94% reported improvement in vaginal rejuvenation, and 100%
reported satisfaction with treatment. VHI improvement remained significant at 6–8 months
after treatments (P 0.01). Most patients (97%) reported no to mild discomfort with treatment.
Responses were mild and transient following treatment, with itching being the most commonly
reported (20%) side effect.
Conclusion: In this study, fractional CO2
laser treatment was associated with improvement of
vaginal health and amelioration of symptoms of VVA, resulting in improved sexual function in
perimenopausal women. Treatment time was quick, and there was minimal discomfort associated
with treatment. Investigation of clinical outcome in a larger study population is warranted.
Keywords: genitourinary syndrome of menopause, vaginal rejuvenation, stress urinary
incontinence, collagen remodeling, sexual dysfunction, vulvovaginal atrophy
Introduction
Although the prevalence varies in early premenopausal to late postmenopausal
women, vulvovaginal atrophy (VVA) is considered to be a common and underre-
ported condition, with nearly 50% of postmenopausal women reporting symptoms.1
Self-reported genital symptoms include dryness, irritation, soreness, and associated
dyspareunia.1–3
According to the Vulvovaginal Atrophy Terminology Consensus
Conference Panel, genitourinary syndrome of menopause (GSM) is a more medically
accurate term for VVA and includes genital symptoms, as well as sexual symptoms of
lack of lubrication, discomfort or pain, and impaired function and urinary symptoms
of urgency, dysuria, and recurrent urinary tract infections.4
Clinical findings include
the presence of pale and dry vulvovaginal mucosa with petechiae.
Thinning of the epithelial lining and loss of lubrication during intercourse contribute
to dyspareunia and can have a detrimental effect on sexual gratification. As sexual
Correspondence: César Arroyo
HM Montepríncipe University Hospital
Laser Unit, C/Senda del Infante 28, 28035
Madrid, Spain
Email carroyoromo@gmail.com
Journal name: International Journal of Women’s Health
Article Designation: Original Research
Year: 2017
Volume: 9
Running head verso: Arroyo
Running head recto: CO2
laser treatment of VVA
DOI: http://dx.doi.org/10.2147/IJWH.S136857
Number of times this ar ticle has been viewed
This article was published in the f ollowing Dove Press journal:
International Journal of Women’s Health
28 August 2017
International Journal of W omen’sHealth Dovepress
O R I G I N A L R E S E A R C H
open access to scientific and medical research
Open Access Full Text Article
Fractional CO2
laser treatment for vulvovaginal
atrophy symptoms and vaginal rejuvenation in
perimenopausal women
César Arroyo
HM Montepríncipe University
Hospital Laser Unit, Madrid, Spain
Background:Thisstudyinvestigatedanovelfractionalcarbondioxide(CO2
)laser for treatment
of symptoms associated with vulvovaginal atrophy (VVA) in perimenopausal women.
Methods: The study included 21 perimenopausal women (mean age 45 7 years) treated three
times by CO2
laser resurfacing and coagulation of the vaginal canal tissue and mucosal tissue of
the introitus. Vaginal health index (VHI) scores were computed by the investigator at baseline
and follow-ups. Subjects reported on sexual function, satisfaction, and improvement with treat-
ment. A visual analog scale was used to measure discomfort with treatment.
Results:Vaginal health andsubject assessment of vaginal symptoms improved with successive
treatments. At 12 weeks following the third treatment, 82%of the patients showed a statistically
significant improvement in VHI (P 0.05). Additionally, 81% of subjects reported improve-
ment in sexual gratification, 94% reported improvement in vaginal rejuvenation, and 100%
reported satisfaction with treatment. VHI improvement remained significant at 6–8 months
after treatments (P 0.01). Most patients (97%) reported no to mild discomfort with treatment.
Responses were mild and transient following treatment, with itching being the most commonly
reported (20%) side effect.
Conclusion: In this study, fractional CO2
laser treatment was associated with improvement of
vaginal health and amelioration of symptoms of VVA, resulting in improved sexual function in
perimenopausalwomen. Treatmenttimewasquick,andtherewasminimal discomfortassociated
with treatment. Investigation of clinical outcome in a larger study population is warranted.
Keywords: genitourinary syndrome of menopause, vaginal rejuvenation, stress urinary
Journal
Article
Year: 20
Volume
Runnin
Runnin
DOI: ht
Number of times this ar ticle has been viewed
This article was published in the f ollowing Dove Press journal:
International Journal of Women’s Health
28 August 2017
© 2017Arroyo.ThisworkispublishedandlicensedbyDoveMedical PressLimited. Thefull termsof thislicenseareavailableat https://www.dovepress.com/terms.php
andincorporatetheCreativeCommonsAttribution– NonCommercial (unported,v3.0) License(http://creativecommons.org/licenses/by-nc/3.0/).Byaccessingtheworkyou
herebyaccept theTerms.Non-commercial usesof theworkarepermittedwithout anyfurther permissionfromDoveMedical PressLimited,providedtheworkisproperlyattributed.For permission
for commercial useof thiswork,pleaseseeparagraphs4.2and5of our Terms(https://www.dovepress.com/terms.php).
International Journal of Women’s Health 2017:9 591–595ss.com
591
7
reported (20%) side effect.
Conclusion: In this study, fractional CO2
laser treatment was associated with improvement of
vaginal health and amelioration of symptoms of VVA, resulting in improved sexual function in
perimenopausalwomen. Treatmenttimewasquick,andtherewasminimaldiscomfortassociated
with treatment. Investigation of clinical outcome in a larger study population is warranted.
Keywords: genitourinary syndrome of menopause, vaginal rejuvenation, stress urinary
incontinence, collagen remodeling, sexual dysfunction, vulvovaginal atrophy
Introduction
Although the prevalence varies in early premenopausal to late postmenopausal
women, vulvovaginal atrophy (VVA) is considered to be a common and underre-
ported condition, with nearly 50% of postmenopausal women reporting symptoms.1
Self-reported genital symptoms include dryness, irritation, soreness, and associated
dyspareunia.1–3
According to the Vulvovaginal Atrophy Terminology Consensus
Conference Panel, genitourinary syndrome of menopause (GSM) is a more medically
accurate termfor VVAand includes genital symptoms, as well as sexual symptoms of
lack of lubrication, discomfort or pain, and impaired function and urinary symptoms
of urgency, dysuria, and recurrent urinary tract infections.4
Clinical findings include
the presence of pale and dry vulvovaginal mucosa with petechiae.
Thinningoftheepithelial liningandlossoflubricationduringintercoursecontribute
to dyspareunia and can have a detrimental effect on sexual gratification. As sexual
rroyo
ity Hospital
ante 28, 28035
.com
Láser
Vaginal CO2 laser for the treatment of vulvovaginal atrophy in women with breast cancer: LAAVA pilot study.
Breast Cancer. Res Treat 2019(3) doi:10.1007/s10549-019-05384-9
Pearson A, Booker A, Tio M, Marx G.
Int J Womens Health. 2017 Aug 28;9:591-595. doi: 10.2147/IJWH.S136857. eCollection 2017. Fractional CO2 laser treatment for vulvovaginal atrophy symptoms and vaginal rejuvenation in perimenopausal women.
Arroyo C
Laser Ther. 2018 Mar 31;27(1):41-47. doi: 10.5978/islsm.18-OR-04. Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy. Eder SE

21.
- Apoya el uso de estrógenos vaginales en mujeres RE/RP
negativas
- No hay datos específicos para grupos separados ER+EP+ o ER-EP-
en términos de efectividad y seguridad en estos grupos
Posicionamiento de la NAMS 2013:
CONTRAINDICADOS
Menopause. 2013 Sep;20(9):888-902; quiz 903-4. doi: 10.1097/GME.0b013e3182a122c2.
Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society.

22.
https://www.acog.org/Clinical-Guidance-and-Publications/Committee-Opinions/Committee-on-
Gynecologic-Practice/The-Use-of-Vaginal-Estrogen-in-Women-With-a-History-of-Estrogen-Dependent-
Breast-Cancer?IsMobileSet=false
ACOG American College of Obstetricians and Gynecologists. Obstet Gynecol 2016;127:e93–6. committee
opinion Number 659, March 2016 (Reaffirmed 2018) The Use of Vaginal Estrogen in Women With a
History of Estrogen-Dependent Breast Cancer

23.
Labrie F, Archer DF, Martel C, et al. Combined data of intravaginal prasterone against vulvovaginal atrophy of menopause.
Menopause. 2017 Nov;24(11):1246-1256.
Sequedad vaginal
Prasterona
Su Ficha Técnica contraindica su uso en pacientes con "Diagnóstico actual,
antecedentes o sospecha de cáncer de mama"

24.
Estrógenos + + + + +
Del Pup et al. Eur Rev Med Pharmacol Sci 2016; 20: 3934-3944

25.
Mejoría sintomática con ospemifeno
Goldstein 2014:CLIMACTERIC 2014;17:173–182

26.
Evidence overview
No diferencias en marcadores de resorción ni formación ósea entre
ospemifeno y raloxifeno en mujeres no osteoporóticas a las 12 semanas de
tratamiento
Adapted from: Komi J, et al. J Bone Miner Metab 2006; 24: 314-8.
NTX: N-terminal cross-linking telopeptide of type I collagen; CTX: C-terminal cross-linking telopeptide of type I collagen.
Marcadores
resorción
Sample
Ospemifene
60mg
Raloxifene
60mg
NTX
(normal range, 5-
65nmol/mmol creatinine)
Before 75.0 ± 43.6 56.3 ± 29.4
Absolute change -20.2 ± 43.4 -10.2 ± 28.0
Percent change -10.2 ± 69.4 -7.9 ± 35.1
Post study 59.3 ± 21.2 49.5 ± 20.7
CTX
(normal range, 40-
680µg/mmol creatinine)
Before 417.3 ± 209.4 304.0 ± 168.5
Absolute change -56.6 ± 118.6 -4.6 ± 137.4
Percent change -9.8 ± 31.5 17.1 ± 93.4
Post study 424.0 ± 230.6 318.8 ± 134.0
Marcadores
formación
Sample
Ospemifene
60mg
Raloxifene
60mg
Bone ALP (normal range,
3.0–14µg/l)
Before 9.9 ± 3.1 9.5 ± 4.5
Absolute change 0.3 ± 2.1 0.6 ± 1.5
Percent change 5.8 ± 19.7 7.4 ± 16.4
Post study 10.6 ± 2.8 10.3 ± 4.2
Osteocalcin
(normal range, 3.8–
30µg/l)
Before 30.0 ± 11.1 26.9 ± 11.4
Absolute change -1.9 ± 7.9 -0.5 ± 6.7
Percent change -0.7 ± 27.1 4.0 ± 27.8
Post study 32.1 ± 8.7 30.8 ± 9.8
PINP
(normal range, 19–
84µg/l)
Before 51.1 ± 23.2 45.5 ± 24.8
Absolute change -2.2 ± 16.3 4.6 ± 15.6
Percent change 3.8 ± 35.2 21.3 ± 42.9
Post study 54.2 ± 18.2 52.4 ± 24.4
PICP
(normal range, 50–
170µg/l)
Before 125.0 ± 35.6 129.2 ± 35.7
Absolute change 0.5 ± 30.5 11.0 ± 36.6
Percent change 3.3 ± 22.1 10.1 ± 27.0
Post study 136.8 ± 31.6 147.6 ± 49.8
Bone ALP: bone-specific alkaline phosphatase; PINP: pro-collagen type I N propeptide; PICP: pro-collagen type I C propeptide.

27.
Martino S, et al. J Natl Cancer Inst 2004;96:1751-1761
Incidencia de cáncer de mama invasivo RE+ y RE-
8 años de MORE y CORE (N=7705)
0
0,5
1
1,5
2
2,5
3
3,5
4
Placebo (N=2.576)
Raloxifeno (N=5.129)
RP 0,24 (95% IC = 0,15 - 0,40)
P <0,001
RP 1,06 (95% IC 0,43 - 2,59)
P = 0,90
Incidencia/1.000mujeres-años
RE+ (n=66) RE- (n=22)
*Las mujeres en la división de Raloxifeno recibieron Rlx 60 ó 120
mg/d en MORE y rlx 60 mg/d en CORE

28.
- Una mujer del grupo placebo
discontinuó por diagnóstico de
cáncer de mama.
- Otra mujer del grupo placebo
presentó un carcinoma in situ
Ningún cáncer de mama en
mujeres con ospemifeno

29.
Incidence of Breast Cancer in Vulvar and Vaginal Atrophy (VVA) Patients Treated With Ospemifene and
Those Without any VVA-Related Treatments From US Real World Data
B. Cai1, S. Djumaeva2, H. Kanakamedala3, M. Particco2, C. Altomare1
1 Shionogi Inc., Florham Park, NJ, USA; 2 Shionogi Limited, London, UK; 3 Genesis Research LLC, Hoboken, NJ, USA
EMAS 2019, Berlin, Germany, May 15–17, 2019
Ospemifene
Group
(N=2,528)
Untreated
Group
(N=118,623)
Incidence
Rate Ratio
(95% CI)
Total number of patients with
breast cancer diagnosis any time
after index date
7 927
Total number of follow-up years
between index date and
enrollment end date
5,560 322,300
Rate of breast cancer per 1000
patients per follow-up year (95%
CI)
1.3
(0.5; 2.6)
2.9
(2.7; 3.1)
0.45
(0.19; 0.84)
Incidence Rate of Breast Cancer
Ospemifene Group
(N=2,005)
Untreated
Group
(N=4,010)
Incidence
Rate Ratio
(95% CI)
Number of breast cancer incidence case 4 14
Total person-year (between index date and enrollment end date) 4,386 8,774
Incidence rate per 1,000 person-year (95% CI) 0.9 (0.2; 2.3) 1.6 (0.9; 2.7)
0.56 (0.22;
0.85)
Incidence Rate of Breast Cancer

30.
RESULTADOS
EFICACIA
Mujeres que mostraron reducción en la severidad de su SMM en la semana 12
OSP PBO
Población general 74,90% 61,80%
Con historia de Cáncer de Mama 66,70% 50,00%
Sin historia de Cáncer de Mama 75,00% 61,90%
Mejoras comparables en los pacientes con OSP tanto CON (n=11) como SIN (n= 1091)
historia de cáncer de mama
o Bruyniks N, Del Pup L, Biglia N. Safety and Efficacy of Ospemifene in Women with A History of Breast Cancer. J Gynecol Women’s Health. 2019: 13(5): 555871.
Research Article
Volume 13 Issue 5 - January 2019
DOI: 10.19080/JGWH.2019.13.555871
J Gynecol Women’s Health
Copyright © All rights are reserved by Nico Bruyniks
J Gynecol Women’s Health 13(5): JGWH.MS.ID.555871 (2019) 001
Journal of
Gynecology and Women’s Health
ISSN 2474-7602
Safety and Efficacy of Ospemifene in Women
with A History of Breast Cancer
Nico Bruyniks1
*, Lino Del Pup2
and Nicoletta Biglia3
1
BrInPhar Ltd, Iver Heath, Buckinghamshire, United Kingdom
2
Centro di Riferimento Oncologico, National Cancer Institue, Italy
3
Department of Oncological Gynaecology, University of Turin, Italy
Submission: December 21, 2017; Published: January 08, 2019
*Corresponding author: Nico Bruyniks, BrInPhar Ltd, Iver Heath, Buckinghamshire, United Kingdom
Background
Vulvar and vaginal atrophy (VVA) is a chronic, progressive
postmenopausal condition characterized by dyspareunia, vaginal
dryness and vaginal irritation, which are a consequence of a
decline in endogenous estrogen production [1]. It has previously
been shown that women with a history of breast cancer are
more likely to have moderate or severe symptoms and signs of
VVA than women without breast cancer, particularly if treated
with aromatase inhibitors [2] or tamoxifen after high-dose
chemotherapy [3]. Due to the risk of breast cancer recurrence
if exposed to estrogen [4], all estrogens (even low-dose vaginal
estrogens) are contra-indicated in women with known, past, or
suspected breast cancer [5].
Ospemifene is an oral non-estrogen treatment that has been
approved for the treatment of moderate to severe symptomatic
VVA in post-menopausal women who are not candidates for
local vaginal estrogen therapy [5,6]. It belongs to the selective
estrogen receptor modulator (SERM) class, which also includes
treatments indicated for the treatment and/or prevention of
certain breast cancers [7-10]. Ospemifene binds selectively
to estrogen receptors to exert a tissue-specific effect [11]. In
the breast, there are two estrogen receptors (ERα and ERβ),
which can bind estrogen or a SERM [12,13]. Preclinical animal
data suggest that ospemifene inhibits malignant breast tissue
growth [14-18]. In addition, data from the ospemifene clinical
Abstract
Background: This post-hoc analysis compares the efficacy and safety data from women with or without a history of breast cancer who
had been enrolled in the ospemifene clinical trial program.
Methods: Efficacy was assessed by the co-primary endpoints of most bothersome symptom (MBS; pooled data from two studies) and
mean baseline to Week 12 change in vaginal pH and maturation index (pooled data from three studies). Safety was assessed using pooled
data from all three studies. Comparisons were made between ospemifene-treated women with a history of breast cancer (≥10 years prior to
enrolment; n=11) versus those without (n=1091).
Result: There were no differences in ospemifene-related improvements in symptoms of vulvar and vaginal atrophy (percentage whose
MBS severity improved by ≥1 point on the 4-point severity scale) and in physiological parameters (vaginal pH, parabasal cells, and superficial
cells) in women with versus without a history of breast cancer. Treatment-emergent adverse events and adverse drug reactions were
comparable in the women using ospemifene who had a previous history of breast cancer (64% and 36%, respectively) compared with those
that who did not (69% and 47%, respectively).
Conclusion: In this small post-hoc analysis, previous history of breast cancer did not appear to affect the efficacy or safety of ospemifene.
Trial registration numbers NCT01585558, NCT01586364, NCT00729469 and NCT00566982.
Keywords: Breast cancer; Dyspareunia; Estrogen agonist/antagonist; Ospemifene; Postmenopausal; Safety; Selective estrogen receptor
modulator; Vulvar and vaginal atrophy
Abbreviatations: ADR: Adverse Drug Reaction; ER: Estrogen Receptor; EU: European Union; FDA: Food and Drug Administration; MBS: Most
Bothersome Symptom; SD: Standard Deviation; SERM: Selective Estrogen Receptor Modulator; TEAE: Treatment-Emergent Adverse Event;
VVA: Vulvar and Vaginal Atrophy

31.
Parámetros fisiológicos: pH, % células parabasales y superficiales en mujeres
tratadas con OSPEMIFENO
Parámetro
Historia de cáncer de mama
Sí (n=11) No (n=1091)
pH
Media de baseline ± DE 6,2±0,7 6,3±0,8
Cambio medio a la semana 12 ± DE -0,8±1,4 -1,0±1,0
Células parabasales (%)
Media de baseline ± DE 71,4±31,0 47,8±40,1
Cambio medio a la semana 12 ± DE -58,8±34,3 -38,1±39,9
Células superficiales (%)
Media de baseline ± DE 0,4±0,8 0,9±2,3
Cambio medio a la semana 12 ± DE 13,5±15,8 11,3±14,4
Las diferencias no fueron significativas por el bajo número de pacientes con historia de
cáncer de mama
DE: Desviación estándar
RESULTADOS
EFICACIA
Research Article
Volume 13 Issue 5 - January 2019
DOI: 10.19080/JGWH.2019.13.555871
J Gynecol Women’s Health
Copyright © All rights are reserved by Nico Bruyniks
J Gynecol Women’s Health 13(5): JGWH.MS.ID.555871 (2019) 001
Journal of
Gynecology and Women’s Health
ISSN 2474-7602
Safety and Efficacy of Ospemifene in Women
with A History of Breast Cancer
Nico Bruyniks1
*, Lino Del Pup2
and Nicoletta Biglia3
1
BrInPhar Ltd, Iver Heath, Buckinghamshire, United Kingdom
2
Centro di Riferimento Oncologico, National Cancer Institue, Italy
3
Department of Oncological Gynaecology, University of Turin, Italy
Submission: December 21, 2017; Published: January 08, 2019
*Corresponding author: Nico Bruyniks, BrInPhar Ltd, Iver Heath, Buckinghamshire, United Kingdom
Background
Vulvar and vaginal atrophy (VVA) is a chronic, progressive
postmenopausal condition characterized by dyspareunia, vaginal
dryness and vaginal irritation, which are a consequence of a
decline in endogenous estrogen production [1]. It has previously
been shown that women with a history of breast cancer are
more likely to have moderate or severe symptoms and signs of
VVA than women without breast cancer, particularly if treated
with aromatase inhibitors [2] or tamoxifen after high-dose
chemotherapy [3]. Due to the risk of breast cancer recurrence
if exposed to estrogen [4], all estrogens (even low-dose vaginal
estrogens) are contra-indicated in women with known, past, or
suspected breast cancer [5].
Ospemifene is an oral non-estrogen treatment that has been
approved for the treatment of moderate to severe symptomatic
VVA in post-menopausal women who are not candidates for
local vaginal estrogen therapy [5,6]. It belongs to the selective
estrogen receptor modulator (SERM) class, which also includes
treatments indicated for the treatment and/or prevention of
certain breast cancers [7-10]. Ospemifene binds selectively
to estrogen receptors to exert a tissue-specific effect [11]. In
the breast, there are two estrogen receptors (ERα and ERβ),
which can bind estrogen or a SERM [12,13]. Preclinical animal
data suggest that ospemifene inhibits malignant breast tissue
growth [14-18]. In addition, data from the ospemifene clinical
Abstract
Background: This post-hoc analysis compares the efficacy and safety data from women with or without a history of breast cancer who
had been enrolled in the ospemifene clinical trial program.
Methods: Efficacy was assessed by the co-primary endpoints of most bothersome symptom (MBS; pooled data from two studies) and
mean baseline to Week 12 change in vaginal pH and maturation index (pooled data from three studies). Safety was assessed using pooled
data from all three studies. Comparisons were made between ospemifene-treated women with a history of breast cancer (≥10 years prior to
enrolment; n=11) versus those without (n=1091).
Result: There were no differences in ospemifene-related improvements in symptoms of vulvar and vaginal atrophy (percentage whose
MBS severity improved by ≥1 point on the 4-point severity scale) and in physiological parameters (vaginal pH, parabasal cells, and superficial
cells) in women with versus without a history of breast cancer. Treatment-emergent adverse events and adverse drug reactions were
comparable in the women using ospemifene who had a previous history of breast cancer (64% and 36%, respectively) compared with those
that who did not (69% and 47%, respectively).
Conclusion: In this small post-hoc analysis, previous history of breast cancer did not appear to affect the efficacy or safety of ospemifene.
Trial registration numbers NCT01585558, NCT01586364, NCT00729469 and NCT00566982.
Keywords: Breast cancer; Dyspareunia; Estrogen agonist/antagonist; Ospemifene; Postmenopausal; Safety; Selective estrogen receptor
modulator; Vulvar and vaginal atrophy
Abbreviatations: ADR: Adverse Drug Reaction; ER: Estrogen Receptor; EU: European Union; FDA: Food and Drug Administration; MBS: Most
Bothersome Symptom; SD: Standard Deviation; SERM: Selective Estrogen Receptor Modulator; TEAE: Treatment-Emergent Adverse Event;
VVA: Vulvar and Vaginal Atrophy
o Bruyniks N, Del Pup L, Biglia N. Safety and Efficacy of Ospemifene in Women with A History of Breast Cancer. J Gynecol Women’s Health. 2019: 13(5): 555871.

32.
Estrógenos + + + + +
Del Pup et al. Eur Rev Med Pharmacol Sci 2016; 20: 3934-3944

33.
Ospemifeno es seguro y efectivo para mejoría salud vaginal
Senshio Ficha Técnica; European Medicines Agency. Senshio Public Assessment Report, 2015

34.
Ospemifeno
Seguridad cardiovascular
Ficha técnica de Ospemifeno: La información detallada de este medicamento está disponible en la página web de la Agencia
Europea de Medicamentos http://www.emea.europa.eu
Constantine et al. Menopause 2015:Menopause: The Journal of The North American Menopause Society Vol. 22, No. 1, pp. 36/43

35.
2019;62(2):141-148

36.
- Menopausia (natural o post-quimioterapia)
- Antecedentes de Cirugía del cáncer de mama
- Antecedentes de Cáncer estrógeno-dependiente tratado con hormonoterapia
- Antecedentes de Cáncer no hormono-dependiente
Deseo de mejorar calidad de vida
(incluyendo sexo y masa ósea)Clinical profile of women with VVA who are not candidates for
local vaginal oestrogen therapy
Nappi RE et al. Minerva Ginecol 2017. 69(4):370-380.
Mujeres Postmenopáusicas con AVV, con antecedentes de cáncer de
mama que hayan terminado su tratamiento, incluyendo el
tratamiento adyuvante:

37.
- Climaterio de difícil manejo
- Cuestión muy pertinente y no bien
resuelta
- Alternativas eficaces disponibles
- Formación e implicación del/la
profesional y la mujer
Manejo de la superviviente al cáncer de mama