Correlation of ER PgR, Her2 expression with reponse to neoadjuvant chemotherapy in breast cancer. Presentation Transcript
NEW DIRECTIONS IN THE TREATMENT OF BREAST CANCERCorrelation between response topreoperative chemotherapy and ER, PgR,HER-2 expression DR IMRANA TANVIR
Preoperative Therapy in Breast Cancer Improves breast conservation (BCS rates improved by 5-10%) Allow early assessment of treatment.
Goals of Preoperative SystemicTherapy in Breast CancerWhat are the optimal markers for various breast cancer phenotypes?Our interest is to allow therapy adjustments to improve outcomeWhen to do therapy, how to determine the need for it, and the need to change treatment ? That’s What Brought me Here Today!
What is a biomarker?-anatomical, physiological, biochemical or molecularparameters associated with the presence and severity ofspecific disease-detectable and measurable by a variety of methodsincluding physical examination, laboratory assays andmedical imaging
A useful biomarker should meet two criteria - Reproducible - Conveys information about the disease.
Potential uses for biomarkers in oncology Screen for disease Distinguish betweenAssess risk of benign versus developing malignant processes disease Biomarker including staging Monitor diseasestatus before and after therapy Predict response to therapy Determine prognosis independent of therapy
Predictive marker predict the magnitude of response to a given treatment Prognostic marker predict inherent disease outcome
What is a Surrogate Outcome? Surrogate outcome Replaces a distal endpoint (e.g., survival) by a proxy endpoint (e.g., clinical or pathologic response, imaging, gene expression, …) Surrogate marker A measure of the surrogate outcome
What is a Surrogate Marker? Must predict clinical outcome, in addition topredicting the effect of treatment on clinicaloutcome Marker Clinical OutcomeAdapted from E. Garrett-Mayer, PhD
Establish an association between marker, treatment, andclinical outcome, in which marker mediates relationshipbetween clinical outcome and treatmentTreatment Marker Clinical Outcome Adapted from E. Garrett-Mayer, PhD
Is a Correlate Marker Also a Surrogate Marker? CLINICAL OUTCOME TREATMENT ? MARKER CLINICALTREATMENT MARKER OUTCOME
Not all markers areappropriate for surrogaterole
Surrogate Markers and Therapy CLINICALTREATMENT MARKER OUTCOME RESPONSE - clinical or path CHEMO .MOLECULARENDOCRINE - proliferation,ANTI HER2 cell LOCAL death, gene CONTROL expression, . epigenetics, SURVIVAL circulating tumor cells, etc … .IMAGING - US, PET, MRI
Is pCR a Surrogate for Survival?Patients who achieve pCR clearly have better survival rates than patients who do not.Feldman LD, et al, Cancer Res46:2578-81, 1986; Fisher B, et al, J ClinOncol16:2672-85, 1998; KuererHM, et al, J ClinOncol17:460-9, 1999
The role of pathological response as a surrogate for survival can be refined by the use of standardized pathology measures after PSTE.g., Residual Cancer Burden (Symmans, ASCO 2006)AJCC TNM after PST (Carey, JNCI 2005)
If pCR rate increases will survival rateincrease too?Is pCR of prognostic value in patients withER+ breast cancer or those treated withendocrine therapy?Can patients who achieve a pCR be treatedwith less therapy? (surgery, RT, adjuvantsystemic treatment)
Breast Cancer is a Mosaic! Predictive Clinical Treatment Marker Outcome TUMOR FEATURES - CHEMO gene expression . LOCAL CONTROL - ER, PR, HER2 ENDOCRINE - . .SURVIVAL pharmacogenetics - ANTI-HER2,various nomograms
Identification of Tumor SubtypesPredictive Clinical Treatment Marker Outcome Selection of Patient Population for Various Therapy Options is Key!
Why ER, PgR, and HER2Tumors completely lacking ER/PgR particularlysensitive to preoperative chemotherapy (CT)HER2 linked with resistance to CT and worseprognosisCan we use these markers to tailor therapy?
OBJECTIVESTo evaluate predictive values of ER PgR and Her-2 inclinical and pathologic response of breast cancerstreated with neoadjuvant chemotherapy.
MATERIALS AND METHODS56 patients with breast cancerPretreatment core biopsy - histologic features.Immunohistochemical stains for ER, PgR,Her2 wereobtained on the initial core biopsy.
Tumor measurements were performed by physicalexamination -at the baseline -after final cycle of neoadjuvant therapy.The pathologic response in the surgical excisionspecimen was performed -Miller Pyane System of classification neoadjuvant chemotherapy
STATUS SUMMARY 0F ER/PgREarly response is an independent predictorof pCR and so may be used to predictlong term survival.Negative hormone receptor status is oneof the predictive markers forresponse to preoperative chemotherapy.
STATUS SUMMARY OF Her2HER-2 positive status is not a consistentpredictor of response to preoperativechemotherapy.Future studies are required.
ConclusionLimited information on tailoring treatment for anindividual patient is available.Patterns of treatment outcome vary in differentsub populations. Major contrast between ER/PgRpositive and ER/PgR negative tumors
Patients with an early cPR(incomplete due to e.g.ER+) might benefit from more intense treatment.Patients with an early cNC are at high medical needfor new treatment options.