PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II

PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II

Nuevo abordaje terapéutico de la neoadyuvancia

Miquel Àngel Seguí Palmer



Neoadjuvant Chemotherapy: Increase in Lumpectomy Rates


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



Rastogi et al. J Clin Oncol 2008

Effect of pCR on Overall Survival

NSABP B-18 NSABP B-27


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


Disease-free Survival Overall Survival


Residual Cancer Burden and Outcome

Symmans et al. J Clin Oncol 2007


The pCR rate to neoadjuvant chemotherapy according to ER status


The pCR rate after neoadjuvant chemotherapy according to intrinsic molecular subtype

*Immunohistochemical definition of molecular subtypes


Survival by pCR in TNBC

Liedtke et al. J ClinOncol 2008


pCR after Neoadjuvant Chemotherapy + Trastuzumab Treatment Predicts Survival

TECHNO Trial

Untch M et al. SABCS 2010

Survival by pCR in HER2+ BC


Progression-free survival by pCR in ER/PR+ BC

Guarneri et al, JCO 2006 Montagna et al. Breast Cancer Res Treat 2010


Residual Cancer Burden and Outcome

Symmans et al. J Clin Oncol 2007

Subset without adjuvant hormone treatment

Subset who received adjuvant hormone treatment


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


Pooled German Neoadjuvant Trials: Association of pCR with Treatment

Characteristics

von Minckwitz et al. Breast Cancer Res Treat 2011


Pros/Cons of Neoadjuvant Therapy


Should We Revisit the Paradigm of Preop vs. Postop Chemo?

Prat and Perou. Nature Medicine 2009




Neoadjuvant Therapy Questions in Hormonally Sensitive BC


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



ACOSOG Z1031

Ellis et al. SABCS 2010


ACOSOG Z1031



Clinical Data from Neoadjuvant Studies Predict Adjuvant Outcomes


ACOSOG Z1031Ki67 changes and Luminal Subtype (PAM 50)



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



Straver et al. Breast Cancer Res Treat 2010

No pCRs if Good 70-Gene Signature


NSABP B-27Gene Expression and Survival

Paik SABCS 2010


Neoadjuvant Therapy Questions HER-2 Positive BC


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?


GeparQuinto Study

Untch et al. SABCS 2010



GeparQuinto Study

pCR(no invasive/non-invasive residual in breast & nodes)

pCRaccording to subtypes

Untch et al. SABCS 2010


NeoALTTO Study

Baselga et al. SABCS 2010


NeoALTTO Study

Baselga et al. SABCS 2010

51.3%46.9%


NeoSphere Study

Gianni et al. SABCS 2010


Gianni et al. SABCS 2010

pCR (no invasive residual in breast)

NeoSphere Study


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


Steger et al. ESMO 2010


Steger et al. ESMO 2010

Capecitabine in the Treatment of Triple-Negative Early Breast Cancer


Sequential taxane and anthracycline-containing neoadjuvant regimens: The sequential order impact

Thiery-Vuillemin et al. The Breast 2011


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


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

2006−03



Neoadjuvant doxorubicin vs docetaxel in TNBC

Antitumor activity in intrinsic subtypes

Martin et al. ASCO 2010


Neoadjuvant Chemotherapy With or Without Bevacizumab: The GeparQuinto Study

von Minckwitz et al. SABCS 2010


Neoadjuvant Chemotherapy With or Without Bevacizumab: The GeparQuinto Study

von Minckwitz et al. SABCS 2010


Neoadjuvant Breast Cancer Randomised Iniparib Studies


• 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


•Despite the weakness of pCR as a surrogate for OS and DFS in the detection of a treatment effect, preoperative chemotherapy is a model to investigate biology and impact of therapy

Order of therapy does not change outcome, but changes

knowledge

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PERSPECTIVAS ACTUALES Y FUTURAS EN EL MANEJO DEL CÁNCER DE MAMA PRECOZ. PARTE II

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