Triple-Negative Ca’s Respond to Optimized Taxane Chemotherapy

November 1, 2006

Gene expression arrayshave extended the identification ofmolecular subtypes of breast cancerbeyond the presence or absence of theestrogen receptor (ER) and revealed themultiplicity of diseases within the breastcancer umbrella that have different prognoses.

CHICAGO--Gene expression arrayshave extended the identification ofmolecular subtypes of breast cancerbeyond the presence or absence of theestrogen receptor (ER) and revealed themultiplicity of diseases within the breastcancer umbrella that have different prognoses.One of these subtypes is theso-called triple-negative form of breastcancer, or basal-like breast cancer, whichoccurs in 10% to 20% of tumors. Such cancers have low expression of HER2,ER, and progesterone-receptor (PR), andare highly proliferative.

The other molecular subtypes arecommonly described as luminal A (ER+,HER2-); luminal B (ER+, HER2+);HER2 (HER2+, ER-), and normal-like(negative for all markers) (see Table onpage 29).

While endocrine and HER2-targetedtherapies have been effective in the treatment of patients with luminal A, luminalB, and HER2 subtypes of breast cancer,only chemotherapy has been an optionfor patients with basal-like breast cancer.

The Good News
"The only treatment is chemotherapy.That's the bad news. The good news isthat it does work," Lisa A. Carey, MD,associate professor of medicine, Universityof North Carolina School of Medicine, The Good News"The only treatment is chemotherapy.That's the bad news. The good news isthat it does work," Lisa A. Carey, MD,associate professor of medicine, Universityof North Carolina School of Medicine, Chapel Hill, said at the 8th AnnualLynn Sage Breast Cancer Symposium.

Less than 10% of patients with luminalA/B or normal-like subtypes of breastcancer have a pathological complete responseto paclitaxel followed by fluorouracil,doxorubicin, and cyclophosphamide(T-FAC) or doxorubicin andcyclophosphamide followed by paclitaxelor docetaxel (Taxotere) (AC-T), comparedwith 26% to 45% of patients with basal-like breast cancer.

In a study of 82 patients treated withT-FAC, a pathological complete responsewas detected in only 2 of 30 (7%) patientswith luminal A/B breast cancer and0 of 10 (0%) patients with normal-likedisease. However, 10 of 22 patients (45%)with basal-like breast cancer had a documentedcomplete response to the regimen,as did 9 of 20 (45%) HER2+patients.

In a study of 107 breast cancer patientswho were treated with AC-T, only4 of 62 (7%) patients with luminal A/Bbreast cancer had a complete response,compared with 9 of 34 (26%) patientswith basal-like breast cancer.

Although patients with triple-negativebreast cancer tend to have greater rates ofrelapse or residual disease, despite beingsensitive to specific chemotherapeuticagents, outcomes for these patients arebeginning to improve, Dr. Carey said, asresearchers build on the results of clinicaltrials that seek to optimize taxane therapyby increasing the frequency of administration.

Patients with ER- tumors, which include basal-like and HER2+/ER- tumorsubtypes, benefited more than those withER+ tumors in a series of recent clinicaltrials, two of which involved the use oftaxanes. The improvement in diseasefree-survival was 63% for patients withER- tumors, compared with 32% for patientswith ER+ tumors in three CALBGtrials: 8541, 9344, and 9741.

CALGB 9344 examined the benefit ofpaclitaxel added to adjuvant AC. A subsetanalysis by ER and HER2 statusshowed no difference in disease-free survivalwhether patients with ER+ and HER2- tumors received paclitaxel or not.Approximately 70% of patients were diseasefree at 10 years in both treatmentand control groups. However, among patientswho had ER- and HER2- orHER2+ tumors, there was about a 10%improvement in disease-free survival withpaclitaxel.

Targeted Therapies
Regarding targeted therapies, subsetanalysis of E2100, a phase III trial ofbevacizumab (Avastin) added to weeklypaclitaxel for metastatic breast cancer,suggested efficacy in triple-negative breasttumors, Dr. Carey said. Predictive modelsof gene expression indicate that dasatinib (Sprycel) may also have a role toplay in the treatment of the triple-negativesubtype of breast cancer, she said. Ofsix genes that predict response to dasatinib,three also are present in the triplenegativeform of breast cancer: ER, PR,and HER2.

(Sprycel) may also have a role toplay in the treatment of the triple-negativesubtype of breast cancer, she said. Ofsix genes that predict response to dasatinib,three also are present in the triplenegativeform of breast cancer: ER, PR,and HER2.