PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II Nuevo abordaje terapéutico de la neoadyuvancia Miquel Àngel Seguí Palmer
Jan 14, 2016
PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II
Nuevo abordaje terapéutico de la neoadyuvancia
Miquel Àngel Seguí Palmer
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Chemotherapy: Increase in Lumpectomy Rates
Nuevo abordaje terapéutico de la neoadyuvancia
Re-excision for patients who underwent initial lumpectomy
(Breast Cancers Between 2 and 4 cm Diameter)
Christy et al. Ann Surg Oncol 2009
Any patient with a tumor greater than 2 cm should be considered for preoperative chemotherapy, even if the surgeon believes that an initial
lumpectomy would be technically feasible
Mauri et al. J Natl Cancer Inst. 2005 EBCTCG Overview. Oxford, September 2006
What we know
Nuevo abordaje terapéutico de la neoadyuvancia
Nuevo abordaje terapéutico de la neoadyuvancia
Rastogi et al. J Clin Oncol 2008
Effect of pCR on Overall Survival
NSABP B-18 NSABP B-27
Nuevo abordaje terapéutico de la neoadyuvancia
How should we define pCR
pCR is a dichotomous endpoint: you either achieve pCR or you do not
Mazouni et al. J Clin Oncol 2007
How should we define pCR
Nuevo abordaje terapéutico de la neoadyuvancia
Disease-free Survival Overall Survival
Nuevo abordaje terapéutico de la neoadyuvancia
Residual Cancer Burden and Outcome
Symmans et al. J Clin Oncol 2007
Nuevo abordaje terapéutico de la neoadyuvancia
The pCR rate to neoadjuvant chemotherapy according to ER status
Nuevo abordaje terapéutico de la neoadyuvancia
The pCR rate after neoadjuvant chemotherapy according to intrinsic molecular subtype
*Immunohistochemical definition of molecular subtypes
Nuevo abordaje terapéutico de la neoadyuvancia
Survival by pCR in TNBC
Liedtke et al. J ClinOncol 2008
Nuevo abordaje terapéutico de la neoadyuvancia
pCR after Neoadjuvant Chemotherapy + Trastuzumab Treatment Predicts Survival
TECHNO Trial
Untch M et al. SABCS 2010
Survival by pCR in HER2+ BC
Nuevo abordaje terapéutico de la neoadyuvancia
Progression-free survival by pCR in ER/PR+ BC
Guarneri et al, JCO 2006 Montagna et al. Breast Cancer Res Treat 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Residual Cancer Burden and Outcome
Symmans et al. J Clin Oncol 2007
Subset without adjuvant hormone treatment
Subset who received adjuvant hormone treatment
Nuevo abordaje terapéutico de la neoadyuvancia
Pooled German Neoadjuvant Trials: Association of pCR with Treatment Characteristics*
* after adjustment for age, tumor stage, grade, type, HR and HER2 status§ effect as estimated for HER2-positive patients
von Minckwitz et al. Breast Cancer Res Treat 2011
Nuevo abordaje terapéutico de la neoadyuvancia
Pooled German Neoadjuvant Trials: Association of pCR with Treatment
Characteristics
von Minckwitz et al. Breast Cancer Res Treat 2011
Nuevo abordaje terapéutico de la neoadyuvancia
Should We Revisit the Paradigm of Preop vs. Postop Chemo?
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Therapy Questions in Hormonally Sensitive BC
Nuevo abordaje terapéutico de la neoadyuvancia
The pCR rate to neoadjuvant chemotherapy according to histology
There is also evidence that breast-conserving surgery is more likely to be unsuccessful at achieving complete excision of the primary lesion
Chemotheraphy versus Hormone Therapy as Neoadjuvant Treatment in Luminal Breast Cancer: GEICAM 2006-03
Even in luminal phenotypes, chemotherapy tends to be more effective than hormonal therapy in the neoadjuvant setting
• Chemotherapy appears to be more effective than hormonal therapy in patients with Ki67 >10%, pre-menopausal and with high Allred score
• Hormonal therapy appears to have similar efficacy to chemotherapy in patients with Ki67 ≤10% and post-menopausal
Alba et al. ASCO 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Nuevo abordaje terapéutico de la neoadyuvancia
Clinical Data from Neoadjuvant Studies Predict Adjuvant Outcomes
Nuevo abordaje terapéutico de la neoadyuvancia
ACOSOG Z1031Ki67 changes and Luminal Subtype (PAM 50)
Ellis et al. SABCS 2010
Nuevo abordaje terapéutico de la neoadyuvancia
ACOSOG Z1031Ki67 changes and Luminal Subtype (PAM 50)
Luminal A and Luminal B tumors are both endocrine responsive but Luminal A is enriched for PEPI-0 patients who may do sufficiently well on AI alone
Ellis et al. SABCS 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Straver et al. Breast Cancer Res Treat 2010
No pCRs if Good 70-Gene Signature
Nuevo abordaje terapéutico de la neoadyuvancia
NSABP B-27Gene Expression and Survival
Paik SABCS 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Herceptin significantly improves pCR rates
MDACC NOAH
Buzdar et al. ASCO 2004 Gianni et al. ESMO 2007
Combined analysis of the cardiac events reported in three prospective, neoadjuvant studies with concurrent use of anthracyclines and trastuzumab in patients with HER2-positive breast cancer
(MDACC, NOAH, GeparQuattro)
Primary endpoint: incidence of CHF and cardiac dysfunction
The concurrent use of an anthracycline based chemotherapy and trastuzumab (583 of 1765 patients) was associated with an
increased risk of cardiac toxicity
OR 1.95, 95% CI 1.6–3.29
44 cardiac events when trastuzumab was added to chemotherapy compared with 28 cardiac events in the chemotherapy only groups
Bozovic-Spasojevic et al. Lancet Oncoll 2011
Neoadjuvant anthracycline and trastuzumab for breast cancer: is concurrent treatment safe?
Nuevo abordaje terapéutico de la neoadyuvancia
Nuevo abordaje terapéutico de la neoadyuvancia
GeparQuinto Study
pCR(no invasive/non-invasive residual in breast & nodes)
pCRaccording to subtypes
Untch et al. SABCS 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Gianni et al. SABCS 2010
pCR (no invasive residual in breast)
NeoSphere Study
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Therapy Questions HER-2 Negative or Triple-Negative BC
Pre-planned analysis to determine benefit of EDC in patients with TNBC breast cancer
ABCSG-24: a randomised phase III study comparing epirubicin, docetaxel and capecitabine to epirubicin and docetaxel as neoadjuvant treatment for EBC
Nuevo abordaje terapéutico de la neoadyuvancia
Steger et al. ESMO 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Steger et al. ESMO 2010
Capecitabine in the Treatment of Triple-Negative Early Breast Cancer
Nuevo abordaje terapéutico de la neoadyuvancia
Sequential taxane and anthracycline-containing neoadjuvant regimens: The sequential order impact
Thiery-Vuillemin et al. The Breast 2011
Nuevo abordaje terapéutico de la neoadyuvancia
Platinum Sensitivity in BRCA1+/TNBC
• Neoadjuvant trials:– Retrospective trial suggests exquisite sensitivity in BRCA1+– Prospective trial in TNBC less clear
Trial Pop’n Regimen N pCR
Byrski BRCA1+ Non-platinum 90 14 (16%)
BRCA1+ CDDP 75mg/m2 x4 12 10 (83%)
Silver Sporadic TNBC CDDP 75mg/m2 x4 26 4 (15%)
BRCA1+ CDDP 75mg/m2 x4 2 2 (100%)
Ryan Sporadic TNBC CDDP 75mg/m2 x 4 + bevacizumab 15 mg/kg
q3wk x3
51 8 (16%)
Byrski, JCO 2009; Silver JCO 2009; Ryan ASCO 2009
Nuevo abordaje terapéutico de la neoadyuvancia
Differential Response of TNBC to Docetaxel and Carboplatin-Based Neoadjuvant Treatment
pCR of the primary tumor in three types of breast cancer
Chang et al. Cancer 2010
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Neoadjuvant doxorubicin vs docetaxel in TNBC
Antitumor activity in intrinsic subtypes
Martin et al. ASCO 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Chemotherapy With or Without Bevacizumab: The GeparQuinto Study
von Minckwitz et al. SABCS 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Chemotherapy With or Without Bevacizumab: The GeparQuinto Study
von Minckwitz et al. SABCS 2010
Nuevo abordaje terapéutico de la neoadyuvancia
Neoadjuvant Breast Cancer Randomised Iniparib Studies
Nuevo abordaje terapéutico de la neoadyuvancia
• PST has been proven safe and as effective as adjuvant therapy.
• Reasonable clinical options when chemotherapy is clearly indicated or when needed to facilitate BCS.
• Although one of the more convincing arguments for PST is its value as an in vivo test for drug sensitivity, the real major advantage of this treatment modality is the increased breast-conservative surgery rate.
• The ability to tailor therapy based on response thus far has failed to live up to promise