Qué es el Cáncer, Cuáles son las Estadísticas en Puerto Rico & Cómo podemos prevenir,detectar y manejar el Cáncer de Seno?

Raúl H. Morales-Borges, M.D. Instituto de Hematologia & Oncologia Ashford

LA VIDA Y LA ESPERANZA SON MUY BONITAS

Y NO PODEMOS NEGARLA.

RHMB 2005

Prevención es lo mejor para gozar de una vida saludable.

RHMB 2005

Cáncer

Cáncer = Cangrejo

Neoplasma = Crecimiento Nuevo

Oncos = Tumor

Características de Tumor Benigno

Crecimiento lento

No invasión a otros tejidos

No metástasis

Características de Tumor Maligno

Proliferación de células neoplásticas

Estroma de soporte

Neovascularización (vasos sanguíneo nuevos)

Invasión y Metástasis

Caminas por el bosque y notas que hay árboles diferentes pero dentro

de la misma clase; a caso todos somos iguales ?

Raul H. Morales-Borges

2005

Grado de Tumores

Grado I – Bien diferenciados

Grado II – Moderadamente diferenciados

Grado III – Pobremente diferenciados

Grado IV - Anaplásticos

Estadíos de Tumores malignos

Depende del tamaño del tumor, nodulos linfáticos y metastasis

Estadio I – pequeño

Estadio II – algo más grande, algunos nodulos

Estadio III – invasión de estructuras vecinas, más nodulos

Estadio IV – metástasis

Qué es la Oncología ?

Es la rama de la medicina que estudia y trata el cáncer.

El Oncólogo estudia un bachillerato con premédica (3-4 años), medicina (4 años) y luego hace residencia en medicina interna (3 años) seguido por sub-especialidad en hematología y oncología (3-4 años).

Estadísticas El cáncer es un problema grande de

salud publica en los Estados Unidos, Puerto Rico y el mundo entero.

Es la segunda causa de muerte en USA. Es el responsible de uno de cuatro muertes.

El cáncer de pulmón es el 2do en lugar tanto en varones com en mujeres en cuanto a incidencia, pero ha disminuído por un 3.3% en los varones y ha aumentado por un 22% en las mujeres.

El cáncer de seno es la segunda causa de muerte, pero se ha demostrado una disminución en la incidencia y en la mortalidad desde el año 2001.

Muertes por Cáncer PR 2002

Hombres2,667

Mujeres1,948Próstata 21%

Pulmón 14%

Colorectal 12%

Estómago 6%

Hígado 6%

Esófago 5%

Páncreas 4%

Linfóma 3%

Leucemia 3%

Laringe 2%

Otras Localizaciones

24%

20% Mama

13% Colorectal

10% Pulmón

7% Estómago

5% Hígado

4% Páncreas

4% Ovario

4% Linfóma

3% Cervix

3% Cuerpo útero, NOS

27% Otras Localizaciones

0

20

40

60

80

100

120

140

160

180

200

1985 1990 1995 2000 2005

Tasa de Muerte por Cancer*, Todas las localizaciones, Puerto Rico 1990-2002

Hombres

Ambos sexos

Tasa por 100,000

Mujeres

*Tasas ajustadas por edad a la población Estándar Millón de PR año 2000.Fuente: Registro Central de Cáncer de PR, 2004

Tasa de Mortalidad por Cáncer*, en Hombres, Puerto Rico,1990-2002

0

5

10

15

20

25

30

35

40

1990 1991 1992 1994 1995 1996 1997 1998 1999 2000 2001 2002

Próstata

Pulmón

Colorectal

Estómago

Hí

Hígado

*Tasas ajustadas por edad a la población Estándar Millón de PR año 2000.Fuente: Registro Central de Cáncer de PR, 2004

Tasa por 100,000

Tasa de Mortalidad por Cáncer*, en Mujeres, Puerto Rico, 1990-2000

0

2

4

6

8

10

12

14

16

18

20

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Mama

Colorectal

Pulmón

Estómago

Hígado

*Tasas ajustadas por edad a la población Estándar Millón de PR año 2000.Fuente: Registro Central de Cáncer de PR, 2004

Tasa por 100,000

Casos de Cáncer en Puerto Rico, 2000*

*Excluye los tumores de piel de células basales y escamosas y el carcinoma in situ de cuello uterino.

Hombres5,156

Mujeres5,131Próstata

32%

Colorectal 13%

Pulmón

7%

Vejiga Urinaria

4%

Estómago

4%

Linfóma

4%

Hígado

4%

Leucemia

3%

Esófago

3%

Laringe 3%

Otras Localizaciones 24%

35% Mama

14% Colorectal

6% Cuerpo útero

4% Cervix

4% Pulmón

4% Linfóma

3% Tiroides

3% Ovario

3% Estómago

2% Leucemia

22% Otras Localizaciones

0

20

40

60

80

100

120

140

160

180

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Tasas de Incidencia de Cáncer* para Hombres, Puerto Rico, 1990-2000

Próstata

Pulmón

Colorectal

Vejiga Uriraria

Estómago

Tasa por 100,000

*Tasas ajustadas por edad a la población Estándar Millón de PR año 2000.Fuente: Registro Central de Cáncer de PR, 2004

*Age-adjusted to the 1970 US standard population.Source: Surveillance, Epidemiology, and End Results Program, 1973-1998, Division of Cancer Control and Population Sciences, National Cancer Institute, 2001.

Tasa por 100,000

Tasas de Incidencia de Cáncer* para Mujeres, Puerto Rico, 1990-2000

0

10

20

30

40

50

60

70

80

90

1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000

Mama

Colorectal

Cuerpo úteroCervix

Pulmón

*Tasas ajustadas por edad a la población Estándar Millón de PR año 2000.Fuente: Registro Central de Cáncer de PR, 2004

Supervivencia relativa de cáncer a 5 años*(%) por localización, Puerto Rico,1987-2002 para ambos sexos

Localización

Todos las localizaciones 34

Seno (mujeres) 54

Próstata 65

Colorectal 28

Cuerpo y útero 49

Vejiga urinaria 50

Cervix 30

Pulmón 5

Estómago 8

Linfóma 35

*La sobrevivencia relativa es a 5 años. Source: Registro Central de Cáncer de PR 2004.

Más estadísticas de PR

13 pacientes de cáncer mueren diariamente en PR (2003).

3 % DE LOS PACIENTES DE CANCER PARTICIPAN EN ESTUDIOS CLINICOS.

Cáncer más frequentes en mujeres en EUA

Seno (mamas)

Pulmón

Colon y recto

Utero (matriz)

Ovarios

Linfoma No Hodgkin

Cáncer más frequentes en varones en EUA

Próstata

Pulmón

Colon y recto

Vejiga urinaria

Melanoma

Linfoma No Hodgkin

Incidencia de Muertes en EUA

Hombres

Pulmón

Próstata

Colon y recto

Pancreas

Linfoma

Leucemia

Esófago

Mujeres

Pulmón

Seno

Colon y recto

Pancreas

Ovarios

Linfoma

Leucemia

Cáncer de seno

Casos nuevos USA 213000 y en PR 1500.

Muertes: 40600

Casos nuevos en varones: 1300

Muertes en varones: 400

Probabilidades de desarrollar: 1 / 8 (PR 1/18)

Cáncer de Seno II

Incidencia 110/100,000

Mortalidad 27/100,000

Primeros casos de cáncer seno: Inglaterra para 1805-1933

Pico es despues de los 40’s, pero se han visto desde los 20’s

2007 Estimated US Cancer Cases*

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder. American Cancer Society, Cancer Facts & Figures 2007

Women 678,060Breast 26%

Lung and bronchus 15%

Colon and rectum 11%

Uterine corpus 6%

Melanoma of skin 4%

Non-Hodgkin’s 4%

lymphoma

Thyroid 4%

Ovary 3%

Kidney and renal pelvis 3%

Leukemia 3%

All Other Sites 21%

2007 Estimated U.S. Cancer Deaths*Women 270,100

Lung & bronchus 26%

Breast 15%

Colon & rectum 10%

Pancreas 6%

Ovary 6%

Leukemia 4%

Non-Hodgkin’s 3% lymphoma

Uterine corpus 3%

Brain and other 2%nervous system

Liver and intrahepatic 2%

bile duct

Types of Breast Tumors

70% to 80% of all breast cancer is infiltrating

ductal carcinoma

Benign (fibrocystic changes)Noninvasive – Stage 0

ductal carcinoma in situ (DCIS) lobular carcinoma in situ (LCIS)

Invasive – Stage I, II, III and IVinfiltrating ductal carcinoma (IDC) infiltrating lobular carcinoma (ILC)

InflammatoryAvailable at: http://www.cancer.gov. Accessed March 19, 2007.

Cáncer de Seno con evidencia de engrosamiento de la piel y cambios

inflamatorios

Cáncer de Seno en Hombre en los 1800’s

SIN LUZ SEGUIREMOS EN LAS TIENIEBLAS

RHMB 2005

RHMB 2005

Prevención, Diagnóstico y Manejo del

Cáncer de Seno

Adapted from American Cancer Society (2006) and Hulka et al. (2001).

Factores de Riesgo Hereditarios

Familiar de Primer ó Segundo Grado a nivel maternal ó paternal

BRCA 1 & BRCA 2

Li-Fraumeni Syndrome

Factores relacionados a los Senos

Enfermedad Fibroquística del Seno

Hiperplasia Atípica

Fibroadenomas, Papillomas, Adenosis

Carcinoma Ductal ó Lobular In Situ

Carcinoma del Seno

Hartmann, L. et al. N Engl J Med 2005;353:229-237

BENIGN BREAST DISEASES

(FIBROCYSTIC BREAST DISEASE)

Otros factores…

Radiación Previa al Pecho

Implantes de Silicon

Campos electromagnéticos

Cigarrillo

Accurate clinical staging for breast cancer has always been considered essential before surgery is undertaken (Sobin & Wittekind, 2002). However, it is important to remember the clinical signs of breast cancer that would invalidate surgical attempts at cure. In these instances, initial referral to a clinical oncologist would be more relevant.

The staging systems currently in use are based on the clinical size and extent of invasion of the primary tumour (T), the clinical absence or presence of palpable axillary lymph nodes and evidence of their local invasion (N), together with the clinical and imaging evidence of distant metastases (M). *For T1–3: 'a' indicates no attachment to underlying muscles; 'b' indicates attachment.

Adapted from Sobin & Wittekind (2002).

The TNM classificatio has been subdivided into four broad categories by the Union Internationale Contre Cancer. *Many expert groups include T2 tumors in stage I.

Adapted from Sobin & Wittekind (2002).

Conocimiento de Receptores Hormonales

cAMP, cyclic AMP; E2, oestrogen; 4-OH-E2, 4-hydroxyestradiol; ER, oestrogen receptor; EGFR, epidermal growth factor receptor; IGF-1, insulin-like growth factor; MAPK, mitogen-actived protein kinase; mRNA, messenger RNA; PI3K, phosphoinositide 3-kinase; mtProteins, mitochrondrial proteins; Shc, Src homology 2 domain-containing protein; pShc, phosphorylated Shc protein; Ras, GTP-binding protein; Raf, serine/threonine kinase; Src, protein tyrosine kinase. Dashed line arrows indicate putative pathways.

Reproduced with permission from Yager & Davidson (2006).

Oestrogens cause activation of various protein kinases, such as mitogen-activated protein kinases (MAPK), and increase levels of second messengers, such as cAMP.EGF, epidermal growth factor; IGF-1, insulin-like growth factor 1; PI3K, phosphoinositide 3-kinase; ERK, extracellular signal-activated protein kinase; JNK, c-jun N-terminal kinase.

Reproduced with permission from Yager & Davidson (2006).

Growth factor reduction of progesterone receptor (PR) via direct inhibition of PR gene transcription and induction of membrane-initiated oestrogen receptor (ER) signalling.E2, oestradiol; ERK1/2, extracellular regulated kinase 1/2; HB-EGF, heparin-binding epidermal growth factor; HER, human epidermal growth factor receptor; IGF-IR, insulin-like growth factor-1 receptor; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; SERM, selective oestrogen receptor modulator; Tam, tamoxifen.

Reproduced with permission from Cui et al. (2005).

Binding of epidermal growth factor (EGF) to the human epidermal growth factor receptor (EGFR) activates a cellular pathway, with induction of phosphorylation by intracellular kinases, leading to nuclear signals that increase cell proliferation.

Based on Lo et al. (2006).

Epidermal growth factor receptor (EGFR) family members are dysregulated in many human cancers, suggesting a pivotal role in tumorigenesis (Grünwald & Hidalgo, 2003).

A tumour's hormone receptor status can be determined by immunohistochemistry. This photomicrograph demonstrates strong positive nuclear staining (brown or black) for oestrogen receptors in an infiltrating ductal carcinoma.`

Reproduced with permission from Dietz J et al. Atlas of Cancer.

Tumours that express ER and/or PR are deemed to be endocrine responsive, while those expressing neither receptor are endocrine unresponsive. ER, oestrogen receptor; PR, progesterone receptor; +, positive (Allred score ≥2); –, negative (Allred score <2); ?, unknown. *Calculated from the Nurses' Health Study (2096 incident breast cancer cases during 1,029,414 person-years of follow-up).

Data from Colditz et al. (2004).

Endocrine responsiveness is an important prognostic marker in breast cancer. ER, oestrogen receptor.

Reproduced with permission from Hess et al. (2003).

All patients were treated with systemic endocrine therapy (tamoxifen in >90%). ER+, oestrogen receptor positive; ER–, oestrogen receptor negative; PR+, progesterone receptor positive; PR–, progesterone receptor negative.

Reproduced with permission from Cui et al. (2005).

Many hormones influence breast development and function, including oestrogens, progesterone, androgens, prolactin, and luteinising hormone-releasing hormone (LHRH). FSH, follicle-stimulating hormone; LH, luteinising hormone; ACTH, adrenocorticotrophic hormone.

Based on Dickson (2000) & Russo and Lamarque (1984).

*The relative risk was calculated with the low-risk group as the reference group. †There is no association between the risk of breast cancer and oophorectomy performed at 35 years of age or older.

Reproduced with permission from Clemons & Goss ( 2001).

Oestradiol and, to a lesser degree, other steroid hormones (e.g., progesterone) drive breast cell proliferation, which facilitates mutation, enhances fixation of mutations or facilitates expression of genetic errors by loss of heterozygosity by defects in DNA repair. Germline mutations in relevant tumour-suppressor genes accelerate the transformation to the malignant phenotype.

Reproduced with permission from Henderson et al. (2000).

*ACI denotes a cross between August and Copenhagen-Irish strains and SENCAR sensitive to carcinogenesis.

Reproduced with permission from Yager & Davidson (2006).

Mamografía : Prueba Estandard para Cernimiento y Detección Tempara

Importancia de la Sonomamografía

El Uso del MRI en el Diagnóstico de

Cáncer de Seno

Cirugía Conservadora del Seno

Nódulo Sentinela

A variety of reconstructive techniques are available today aimed at minimising the mutilation effect of mastectomy without compromising the oncological clearance (Ahmed et al, 2005).

(A) A schematic representation of the post-operative appearance after transverse rectus abdominis myocutaneous (TRAM) flap reconstruction. (B) A 35-year-old patient after skin-sparing mastectomy and immediate TRAM.

Reproduced with permission from Dietz J et al. (2002).

(A) A schematic representation of latissimus dorsi (LD) flap breast reconstruction. (B) A 38-year-old patient after modified radical mastectomy with immediate reconstruction using the LD flap and submuscular saline implant.

Reproduced with permission from Dietz J et al. (2002).

Data from Gazet et al. (1991,1996).

Careful attention to histopathology and quality assurance of treatment delivery is essential to ensure APBI is applied appropriately. To this end, both the American Brachytherapy Society (Arthur et al., 2002) and the American Society of Breast Surgeons (ASBS, 2003) have published recommendations for patient selection criteria for accelerated partial breast irradiation (APBI).

The EBCTCG confirmed that polychemotherapy produced substantial and highly significant proportional reductions in relation to the risk of relapse and death from breast cancer. The effects of treatment were described as either proportional or absolute benefits. For women under 50 years at randomisation, the absolute reduction in risk of relapse was 10.4% for node-negative and 15.4% for node-positive disease. The reduction was also significant for mortality (absolute improvements in 10-year survival of 5.7% and 12.4% for node-negative and -positive disease, respectively). CMF, cyclophosphamide, methotrexate and 5-fluorouracil.

Reproduced with permission from the EBCTCG (2005).

AC, doxorubicin, cyclophosphamide; FAC, 5-fluorouracil, cyclophosphamide, doxorubicin; FEC, 5-fluorouracil, cyclophosphamide, epirubicin; HR, hazard ratio; OS, overall survival; T, docetaxel; TAC, docetaxel, doxorubicin, cyclophosphamide; TC, docetaxol, cyclophosphamide.

Data from Nabholtz et al. (2002), Jones et al. (2003), Roche et al. (2004), and Bear et al. (2003).

AC, doxorubicin, cyclophosphamide; HR, hazard ratio; OS, overall survival; T, paclitaxel.

Data from Henderson et al. (2003) and Mamounas et al. (2003).

Following the success of trastuzumab in metastatic breast cancer, four large international multicentre trials were designed to test the efficacy of trastuzumab as adjuvant treatment either with or following chemotherapy. *Group B from N9831 and Group A from HERA were excluded from the analysis. AC, doxorubicin, cyclophosphamide; LN, lymph node.

Data from Romond et al. (2005), Piccart-Gebhart et al. (2005), and Slamon et al. (2005).

Adapted from Piccart et al. (2005).

There are international consensus guidelines based on clinicopathological features and outcomes, which are regularly updated to help inform local guidelines and individual clinicians. The 2005 St Gallen guidelines have defined low-, intermediate- and high-risk categories.

The 2005 St Gallen guidelines recommend adjuvant treatment according to risk and endocrine responsiveness.*Depending on clinician and patient discussion. ET, endocrine therapy; CT, chemotherapy.

Adapted from Piccart et al. (2005).

AC, doxorubicin, cyclophosphamide; CAF, cyclophosphamide, doxorubicin, 5-fluorouracil; CEF, cyclophosphamide, epirubicin, 5-fluorouracil; CMF, cyclophosphamide, methotrexate, 5-fluorouracil; CT, chemotherapy; FEC, 5-fluorouracil, cyclophosphamide, epirubicin; TAC, docetaxel, doxorubicin, cyclophosphamide.

Adapted from Piccart et al. (2005).

Gracias …