El tratamiento del cáncer de mama en la mujer anciana desde un punto de vista multidisciplinar, teniendo en cuenta los factores riesgo/beneficio, la comorbilidad asociada a la paciente y el tratamiento, y las posibles alternativas al tratamiento convencional

1. CANCER DE
MAMA EN EDAD
AVANZADA
Dra. A. Moreno Elola
Hospital Clínico San Carlos
Universidad Complutense de Madrid

2. FACTORES A CONSIDERARFACTORES A CONSIDERAR
◦ Uno de los más importantes FR
para CM es la edad
◦ La edad media de diagnóstico
es 60 a.
◦ El 40% de los cánceres se
diagnostican en >=65 a.
◦ En 2030, el 20% de la población
tendrá >=65 a.
File:Age-Specific SEER Incidence Rates, 2003-
2007 Breast Cancer.svg

3. M. Joerger . Treatment of breast cancer in the elderly: A prospective, population-based
Swiss study Journal of Geriatric Oncology, V4, 2013,39-47
ESTADO ACTUALESTADO ACTUAL
MAYOR PORCENTAJE DE
◦Diagnóstico tardío
◦Estadificación incompleta
◦Tratamiento incorrecto
◦Mayor mortaliad
Breast cancer incidence and mortality
TRATAMIENTO ODDS
RATIO
CC O.37
GC 0.58
RT postCC 0.04
HT ady 0.23
• CLAM
• M1

4. EVIDENCES

5. Barbara L. Van Leeuwen at the MD Anderson Cancer Center, Houston, TX,
The effect of under-treatment of breast cancer in women 80 years
of age and older Review Article
Critical Reviews in Oncology/Hematology, V79, 2011, 315-320
◦ 212 pac mayores de 80 a. Edad mediana=83.5 years
(rango 80–97).
◦ La SV global fue de 7.28 a con un seguimiento mediano
de 4 a.
◦ El 57% de las pacientes fueron infratratadas según los
protocolos nacionales
•Las pacientes que recibieron solo HT comparadas
con la que recibieron tto multimodal demostraron una
disminución en la SV (P < 0.001 )
•Las pacientes sometidas a CC sin RT
sufrieron más recidivas locorregionales (P = 0.045).
•Las pacientes con estudio axilar quirúrgico
presentaron mejor SV (P = 0.04).
TRATAMIENTO EN LA ANCIANA

6. BIOLOGIA TUMORALBIOLOGIA TUMORAL
◦ La mayor parte son RE+ (82.3% ) con factores de baja agresividad.
◦ Existen porcentajes menores de pacientes con tumores más agresivos: RH - =17% , Triple neg=11.4%.
◦ Existe menor porcentaje de pacientes HER2+ =12.0%
Tumor type Percentage of cases
Basal-like 13
HER2 13
Luminal B 28
HER2 status in elderly women with breast cancer Original Research Article
Journal of Geriatric Oncology, V 4, 2013, 362-367. Heather S. Laird-Fick

7. MORTALIDADMORTALIDAD
◦ Desde 1990, las tasas de muerte por CM
han disminuído , pero no para mujeres
mayores de 75 a.
◦ Entre 1990-2007 esta tasa ha disminuído
un 2.5% por a. en la población gral., en
mayores de 75a. ha disminuído solo un
1.1% por a.
◦ La disminución en el RR de muerte por
CM a los 10 a. es el doble en mujeres de
50–64 a. que en mayores de 75 (15.3 vs
7.5%)
◦ En Europa, entre 1990–1994 and 2000–
2004, la mortalidad por CM disminuyó
13% en total. Estratificando por edades,
la disminución fue mucho mayor para
mujeres de 35–64 a.,(17%), comparado
con un 6% para mujeres ≥65 a.

8. SCREENINGSCREENING
◦ Uno de los mayores determinantes de la SV de CM es el screening.
◦ No hay suficientes datos para recomendar el screening
mamográfico.
◦ La ACS (American Cancer Society) no determina edad de
terminación de screening.
◦ La US Preventive Services Task Force ha determinado que para
mujeres ≥74 years,
◦ La AGS (American Geriatrics Society)lo basa en la expectativa de
vida > de 5 a.

9. QUE NOS PREOCUPA?QUE NOS PREOCUPA?
TOXICIDAD POTENCIALTOXICIDAD POTENCIAL
◦ Mayor riesgo por alteraciones fisiológicas
◦ Alteración en absorción de drogas (alteración de
indice de grasa corporal, deshidratación)
◦ Alteración en eliminación de tóxicos (insuficiencia renal
ó hepatica)
◦ Riesgo cardíaco, hematológico y neurológico mayor
◦ Presencia de comorbilidades y politratamientos que
interaccionan con la QT.
◦ Dependencia funcional

10. QUIMIOTERAPIA EN ANCIANASQUIMIOTERAPIA EN ANCIANAS
◦ Tiende a ser menos agresiva
◦ Tiende a no indicarse ó indicarse menos, aunque los efectos
terapeúticos son similares a los de las pacientes jóvenes
◦ El infratratamiento se asocia a peores resultados
◦ Tienden a no incluirse en estudios (aunque la edad avanzada
no es un factor decisivo en la negativa a entrar en estudios) 68%
of younger patients were offered a clinical trial compared with
only 34% of older patients
◦ Con una expectativa de vida minima de 6 años se debe ofrecer
un tratamiento curativo.
Edad Expectativa de vida
65 19
75 12
85 6

11. EDAD BIOLOGICAEDAD BIOLOGICA
◦ La paciente mayor de 70 años suele presentar como mínimo tres
comorbilidades asociadas.
◦ A mayor número de comorbilidades menor expectativa de vida
◦ A los 75 años la esperanza de vida puede variar entre 7.3 años y
12 años dependiendo del número de comorbilidades asociadas.
◦ La Edad Biológica se refiere la clasificación del estado de la
paciente en base a la detección de comorbilidades asociadas
a la edad croólógica, y nos puede dar una indicación de
tratamiento más ó menos agresivo.

12. COMORBIDITIESCOMORBIDITIES
◦ ]
In a large observational cohort
study from Denmark, the presen-
ce of comorbidities, as measured
by the Charlson Comorbidity
Index, was demonstrated to be
an independent adverse prog-
nostic factor in breast cancer
patients aged 50–79 years.

13. COMORBIDITY INDEXCOMORBIDITY INDEX
También se puede utilizar para valorar la utilidad de prevenir un
segundo cáncer.

14. FITNESSFITNESS
◦ Defined as
◦ Better estimated with collaboration between oncologists
and geriatricians
◦ Full geriatric assessment can
• life expectancy of at least 5 years,
• good performance status,
• living independently,
• freely ambulant,
• no significant hepatic, renal, cardiac, respiratory
or metabolic disorders.
•more accurately determine a patient's biological age,
•detect functional deficits that may be missed on routine
oncological review.

15. COMPREHENSIVE GERIATRIC ASSESSMENTCOMPREHENSIVE GERIATRIC ASSESSMENT
(CGA)(CGA)
◦ Is designed to capture details regarding the physical,
nutritional and psychological functioning of an older person,
and can help to more accurately determine biological
patient age.
◦ Detection of areas of functional deficit may then guide
management of reversible deficits.
◦ Has been shown to be an independent predictor of survival
irrespective of tumor type or performance status.
◦ Can identify older breast cancer patients who are potentially
fit enough for adjuvant chemotherapy, who otherwise would
not be treated based on chronological age.
◦ The International Society of Geriatric Oncology recommends
incorporation of CGA, and moreover suggests use of serial
geriatric assessments, to identify incident deterioration, for
which interventions could then be instigated.

16. CGA

17. GERIATRIC 8 ASSESSMENT
◦ The Geriatric 8 (G8) frailty screening tool,
◦ which includes age and
◦ components of the mininutritional assessment and
◦ is scored from 0 (poor) to 17 (good),
◦ was developed from a prospective study of 364 cancer
patients aged ≥70 years, and
◦ demonstrated sensitivity and specificity of 90 and 60%,
respectively, compared with CGA.
◦ The European Organisation for Research and Treatment of
Cancer has considered G8 a suitable screening tool for
incorporation in future clinical trials.

19. M.E. Hamaker Baseline comprehensive geriatric assessment is associated with toxicity
and survival in elderly metastatic breast cancerpatients receiving single-agent
chemotherapy: Results from the OMEGA study of the Dutch Breast Cancer Trialists'
GroupOriginal Research Article The Breast, V23, 2014, 81-87
◦ 78 patients (median age 75.5 years, range 65.8–86.8 years), 73
were evaluable for CGA
◦ 71% had one or more geriatric conditions.
◦ Polypharmacy was the only individual factor significantly
associated with toxicity (p = 0.001).
◦ Conclusion
In elderly patients for whom chemotherapy is being considered, a
CGA could be a useful addition to the decision-making process.
GERIATRIC
CONDITIONS
PERCENTAGE OF GRADE 3-4
TOXICITY
P
NO 19 0.002
2 56
3 or more 80

20. QUIMIOTERAPIA

21. QT EN PACIENTES RE NEGQT EN PACIENTES RE NEG
REVIEW OF DATA FROM THE NATIONAL CANCER INSTITUTE
SURVEILLANCE, EPIDEMIOLOGY AND END RESULTS (SEER)
DATABASE
◦ En 40,000 pacientes >=65 years con CM precoz
◦ Solo el 11% recibieron QT
◦ Pac RE+: No beneficio
◦ Pac RE-; N+: Beneficio para Sv específica HR: 0.72; 95% CI: 0.54–
0.96 y Sv global HR: 0.65; 95% CI: 0.52–0.82 .
◦ La QT confiere un 17% de reducción del riesgo relativo de
muerte (HR: 0.83; 95% CI: 0.74–0.92).
Paolo Carli, Target therapy in elderly breast cancer patients Critical Reviews in Oncology /
Hematology, V83, 2012, 422-431

22. STANDARD CHEMO.STANDARD CHEMO.
◦ En pacientes ER neg la poliquimioterapia mejora de SLE a los 3 años
(85 vs 68%) (p= 0.001).
◦ La selección de pacientes por el CGA permite a las pacientes añosas
obtener tanto beneficio de la QT como las pacientes jóvenes.
◦ El infratratamiento puede llevar a malos resultados pronósticos
Breast cancer in the elderly—Should it be treated differently? Reports of Practical Oncology &
Radiotherapy, V18, 2013, 26-33. Petra Tesarova
CALGB 49907—A randomized trial of adjuvant chemotherapy with standard regimens,
cyclophosphamide,
methotrexate and fluorouracil – (CMF) or doxorubicin and cyclophosphamide – (AC), versus
capecitabine in women 65 years and older with node positive or node-negative breast cancer

23. STANDARD CHEMO.STANDARD CHEMO. TAXANESTAXANES
for the use of polychemotherapy in older breast
cancer patients, as well as validating use of a
nonanthracycline-based regimen
In the US Oncology 9735 study comparing adjuvant AC with
docetaxel/cyclophosphamide (TC), after 7 years median follow-up,
treatment with TC
(DFS: HR: 0.74; p = 0.033; OS: HR: 0.69; p = 0.032).

24. ANTHRACYCLINES. CONGESTIVE CARDIAC FAILURE (CCF)
AND ACUTE MYELOID LEUKEMIA (AML).
◦A high Charlson Comorbidity Index score was
the only other independent predictor of AML
risk (HR: 1.6; 95% CI: 1.3–2.0), highlighting again
the importance of comorbid status in
prognosis and outcomes.
CONCLUSIONS:
◦Selection of a nonanthracycline-based
regimen in elderly patients if possible.
◦More treatment-related deaths were evident
in older patients.
Anthracycline use No QT
10-year rate of CCF 47% 28%
Absolute risk of developing AML at 10
years after QT
1.8 1.2%,

25. Adjuvant trastuzumab in elderly with HER-2 positive breast cancer: A
systematic review of randomized controlled trialsReview Article
Cancer Treatment Reviews, Volume 39, Issue 1, February 2013, Pages 44-50
Janaina Brollo
◦ Eficacia del tto (QT+Trastuzumab vs. QT alone)= 47%
disminución del RR de recidiva en pac con Trastuzumab
(Hazard Ratio: 0.53; 95% CI, 0.36–0.77).
◦ El porcentaje de pacientes con efectos secundarios
cardiacos en el grupo tratado con trastuzumab es del 5%
(95% CI, 4–7%).
◦ Es fundamental contar con un CGA para identificar a las
pacientes de riesgo.
HER 2+ : TRASTUZUMABHER 2+ : TRASTUZUMAB

26. PACIENTES AÑOSAS CON AFECTACIONPACIENTES AÑOSAS CON AFECTACION
AXILARAXILAR
◦ PACIENTES TRIPLE NEG: Poliquimioterapia. Pueden obtener las
mismas ventajas de la QT que las jóvenes. Hacer CGA.
◦ Beneficio de QT solo en pacientes con buen GA
◦ No estudios en mayores de 80 a.
◦ PACIENTES CON TUMORES INTERMEDIOS: Estudio de perfil
genético con plataformas Oncotype DX® (Genomic Health,
CA, USA).
◦ PACIENTES RE+: Tamoxifeno, IA
En pacientes mayores de 65 años con tumores RE+ N+, la
comparación de TAM vs TAM+CMFx3
Demostró mayor toxicidad grado 3 derivada de CMF (17 vs 7%),
Mayor número de muertes por CMF

27. CIRUGIA

28. SURGERYSURGERY
◦ 256 consecutive cases of symptomatic breast cancer in a
population of over 75 years of age.
◦ 142/256 patients underwent surgical intervention in the form of
breast conserving surgery or mastectomy, 114/256 did not.
Matei Dordea Surgery for breast cancer in the elderly – How relevant?
Original Research Article. The Breast, V20, I2011,212-214
•Mean follow up was 6.4 years.
•Our results show a statistically significant association between surgery
and survival (p = 0.05, CI 0.00046–0.19641)
•and a strong statistically significant association between surgery
and disease progression/recurrence (p = 0.001, CI 0.08713–0.03145).
•surgical treatment with adjuvant endocrine and/or radiotherapy was
associated with a statistically significant advantage in terms of disease
related mortality and local disease control

29. ◦ En las pacientes añosas la omisión de cirugía aumenta a partir
de los 80 años de edad (p < 0.05).
◦ El (92%) de las pac que no se operan son tratadas con HT
◦ El 32% de las pacientes revocaron el consentimiento de
cirugía
◦ El 34% de las pacientes que fallecieron lo hicieron por ca de
mama
◦ La sv mediana fue de 2.3 years (rango 0.2–10.7)
◦ El infratratamiento puede influir en el peor pronóstico.
◦ Es adecuado supeditar la indicación a los GA
Marije E. Hamaker Omission of surgery in elderly patients with early
stage breast cancer Original Research Article European Journal
of Cancer, V49, 2013,545-552
INDICACION DE CIRUGIA EN PACIENTES AÑOSASINDICACION DE CIRUGIA EN PACIENTES AÑOSAS

30. HORMONAL

31. Stefan Glück Aromatase inhibitors in the treatment of elderly women with
metastatic breast cancer Original Research Article The Breast, V22,
2013, 142-149
◦ Pacientes mayores de 65 con tumores M1 .
◦ El tto QT es tolerado en pacientes según niveles en el GA,
el cual puede identificar pacientes según un score y guiar
el tto.
◦ En casos de tumores RE+ se acepta el tto endocrino como
primera línea.
◦ En estos casos el tto más eficaz son los IA
◦ Para obtener guías de tto deberían incluirse más
pacientes añosas en estudios de investigación
PACIENTES CON METASTASIS A DISTANCIA

32. Neoadjuvant hormonal therapy for endocrine sensitive breast cancer:
A systematic review Cancer Treatment Reviews, V40, 2014, 86-92
A. Charehbili, D.
◦ considered to be a suitable option for hormone receptor (HR)positive
patients who are unfit for chemotherapy or surgery,
◦ and is increasingly being utilized to achieve tumor downsizing before
surgery in postmenopausal women.
◦ NHT demonstrated similar efficacy to neoadjuvant chemotherapy (NCT) in
HRpositive breast cancer patients.
◦ Clinical responses ranged from 13.5% to 100%, with treatment periods
between 3 and 24 months.
◦ In studies comparing tamoxifen with aromatase inhibitors, the latter were
superior in terms of tumor response and rates of breast-conserving surgery
(BCS).
◦ In most studies with treatment durations longer than 3 months, tumor
response rates increased. Therefore, longer durations of NHT are feasible
and should be considered as an alternative to NCT in selected patients
TRATAMIENTO NEOADYUVANTE EN RE+TRATAMIENTO NEOADYUVANTE EN RE+

33. Kirsten A. Nyrop Feasibility and promise of a 6-week program to encourage physical
activity and reduce joint symptoms among elderly breast cancer survivors on
aromatase inhibitor therapy Original Research Article
Journal of Geriatric Oncology, December 2013
◦ N=20 pacientes con ca mama en tto con IA
◦ Edad media= 71 (65–87). Entrenamiento de 6 semanas
TRATAMIENTO CON IA. COMO MEJORAR EL CGATRATAMIENTO CON IA. COMO MEJORAR EL CGA
Pacientes que
caminaban >20
Aumentó un 30% (p < 0.001).
Dolor articular Disminuyó un 10% (p = 0.63),
Fatiga Disminuyó un 19% (p = 0.31),
Inflamación articular Disminuyó un 32% (p = 0.07).

34. RADIOTERAPIA

35. Francesco Fiorica, Adjuvant radiotherapy on older and oldest breast cancer
patients after conservative surgery: A retrospective analysisOriginal
Research Article
Archives of Gerontology and Geriatrics, V55, 2012, 283-288
PACIENTES MAYORES DE 75 AÑOS
◦ SV a los 5 a. 78.8%. SVLE a los 5 años 89.6%.
◦ Las pacientes con menos co-morbilidad( GA) tienen mayor SV
(p < 0.0001).
◦ No hay diferencias en la toxicidad por Rt respecto a niveles de
comorbilidad ni edad
◦ El tto RT clásico tras CC se puede indicar a cualquier edad y en
pacientes con comorbilidad
◦ Sin embargo la esperanza de vida baja podría disminuir el
beneficio esperado con la RT
RT TRAS CCRT TRAS CC

36. E. Warner, E. Chow Attitudes of Canadian Radiation Oncologists towards
Post-lumpectomy Radiotherapy for Elderly Women with Stage I Hormone-
responsive Breast Cancer Original Research Article
Clinical Oncology, V22, 2010, 97-106
FACTORES A TENER EN CUENTA EN ORDEN DE IMPORTANCIA:
◦ 1. Contraindicación de RT
◦ 2. Salud global de la paciente
◦ 3. Preferencia de la paciente
◦ 4. y 5. Margen libre y tto hormonal
DE LOS MÉDICOS CONSULTADOS:
◦ El 60% de los oncólogos le ofrecerían a la paciente la
decisión
◦ 12–57% no radiarían en edades avanzadas
◦ 64% de los oncólogos desearían tener más información
para estas pacientes
ACTITUD DEL ONCOLOGO PARA INDICAR RTACTITUD DEL ONCOLOGO PARA INDICAR RT

37. Nengliang Yao, Survival after partial breast brachytherapy in elderly patients
with nonmetastatic breast cancer Original Research Article.
Brachytherapy, V12, 2013, 293-302
◦ A sample of 29,647 female patients diagnosed with
nonmetastatic breast cancer in 2002–2007 treated with breast-
conserving surgery and radiotherapy
◦ During a median followup of 3.6 and 4.8 years,
◦ 123 (7.7%) and 3438 (13.6%) patients died after APBI-Brachy and
WBI, respectively.
◦ Recurrence-free survival (p = 0.9711) and overall survival rates
(p = 0.0551) did not differ significantly between the two radiation
modalities.
◦ After accounting for tumor characteristics, patient
characteristics, community factors, and comorbidities, the
recurrence-free survival (hazard ratio, 1.05; 95% confidence
interval, 0.90–1.23; p = 0.5125) and overall survival (hazard ratio,
0.87; 95% confidence interval, 0.72–1.04; p = 0.1332) rates were still
not significantly different between patients treated with APBI-
Brachy and WBI.
RT PARCIAL (ABPI-Brachy)RT PARCIAL (ABPI-Brachy)

38. Alice Goodman Can Postoperative Radiotherapy Be Avoided in Older
Women With Early Breast Cancer and High Estrogen Receptor Expression?
January 15, 2014, Volume 5, Issue 1 ASCO 2014
For RE+ N0 lesions
◦ RT is associated with a very modest gain in local control (2.4%)
in women treated with whole breast irradiation compared to
those in whom it was omitted (0.8% vs 3.2%, respectively, P = .
003).
◦ Postoperative whole-breast irradiation can be safely omitted in
some women aged 65 or older with node-negative, hormone
receptor–positive breast cancer, tumors measuring up to 3 cm,
and high estrogen receptor expression
◦ Compliance with hormone therapy is important
OMISSION OF RT AFTER BCTOMISSION OF RT AFTER BCT

39. CONCLUSIONES
◦ Older women can benefit as much from adjuvant chemotherapy
as younger women, although they have an increased risk of
toxicities.
◦ Decisions regarding adjuvant chemotherapy should be made
based on tumor biology and biological age, rather than
chronological age.
◦ Geriatrician assessment can detect subtle functional deficits that
may impact on the ability of the patient to tolerate
chemotherapy
◦ Future advances should incorporate more accurate and efficient
means for determining the biological age of elderly breast
cancer patients, which will better define the risk:benefit ratio of
adjuvant chemotherapy.

40. CONCLUSIONESCONCLUSIONES
◦ Older women with biologically aggressive breast cancer, in particular
ER-negative disease, stand to gain as much benefit from adjuvant
chemotherapy as younger women. However, the data in support of
this are limited to fit elderly patients, with few, if any, comorbidities.
Even in this select patient group, increased toxicities from
chemotherapy may be seen.
◦ There is a critical need for further research into the appropriate
management of elderly breast cancer patients. CGA remains the
gold standard for predicting biological age and relative frailty of
older breast cancer patients.
◦ No biomarker has yet been identified that can effectively measure
the biological aging process.

41. FUTURE PRESPECTIVESFUTURE PRESPECTIVES
◦ A major difficulty in the identification of an aging biomarker is that most
data are derived from observational studies, and biomarker expression
often correlates with an underlying disease process.
◦ Aging biomarker development may be enhanced through utilization of
metabolomics. The study of the metabolome, that is, study of the myriad
of metabolites that are the end products of complex physiological and
pathological processes, is a relatively new science, but one with
considerable potential applications in the field of oncology, including
early diagnosis, and monitoring of drug treatment response or drug
toxicity.
◦ Furthermore, changes in metabolites with aging may be detectable in
metabolomic profiles, creating an aging metabolomic 'footprint'. In a
comparison of metabolomic profiles of young and old mice, clear
differences were observed, particularly relating to glucose and fatty acid
metabolism, and levels of certain amino acids.
◦ While these results are preliminary, they highlight the potential for
biochemical or metabolic assessment of aging. Extrapolation of aging
biomarkers or metabolomics into oncology remains theoretical at present,
but would potentially provide an important tool for predicting patients
more at risk of adjuvant chemotherapy toxicities.

42. SUGGESTED READINGS
◦ Breast cancer in the elderly: the role of adjuvant radiation
therapy Review Article
Critical Reviews in Oncology/Hematology, Volume 48, Issue
2, November 2003, Pages 165-178
Patrizia Olmi, Carlo
◦ The management of osteoporosis in breast cancer
survivors Review Article
Maturitas, Volume 73, Issue 4, December 2012, Pages 275-279
Pamela Taxel
◦ Challenges in the Treatment of Older Breast
Cancer Patients Review Article
Hematology/Oncology Clinics of North America, Volume 27, Issue
4, August 2013, Pages 785-804
Grant R. Williams