Early-stage breast cancer: Challenging conventional wisdom
31 January 2010—During the second day of the 4th International Breast Cancer Conference (IBCC4) in Paris, presentations focused on clinical updates and the role of histopathology and biology in the management of early-stage breast cancer.
Plenary Session II was introduced by Wolfgang Eiermann, MD (Munich and Red Cross Women Hospital, Munich, Germany), who emphasized that breast cancer is a heterogeneous disease comprising different molecular subtypes based on gene/protein expression profiling, and that individualization of the therapeutic decision-making process is necessary for improved outcomes in patients with breast cancer. Sandra Swain, MD (Washington Cancer Institute, Washington, DC, United States), focused her presentation on the question of whether the maximum potential of chemotherapy for unselected subsets of patients had finally been reached, and Martine Piccart-Gebhart, MD, PhD (Jules Bordet Institute, Brussels, Belgium), outlined four important clinical challenges in patients with hormone receptor (HR)–positive breast cancer, and addressed each issue with new developments in this large patient population. The session concluded with a lively panel discussion, moderated by Ian E. Smith, MD, FRCP, FRCPE (The Royal Marsden Hospital, London, United Kingdom), that focused on the question, “Which patients with HR-positive, early-stage breast cancer need chemotherapy?”
Plenary Session III began with Miguel Martin, MD, PhD (San Carlos University Hospital, Madrid, Spain), giving a brief overview of the current demographics of node-negative breast cancer, as well as common myths surrounding this patient population. This was followed by a new look at node-negative breast cancer provided by Nadia Harbeck, MD (University of Cologne, Cologne, Germany), and presentation of the clinical applications of histology and biology from the view of a pathologist, Frédérique Penault-Llorca, MD (Centre Jean Perrin, Clermont-Ferrand, France).
The following highlights, including recently reported clinical trial data, were presented during Day 2 of IBCC4:
A recent meta-analysis of 12 randomized clinical trials confirmed that adjuvant docetaxel-based chemotherapy was associated with an improvement in disease-free survival (DFS)—regardless of nodal status, expression of hormone receptors/HER2, or age—compared to regimens without taxanes.
Eight-year follow-up of PACS-01 confirmed benefit in DFS and overall survival (OS) with sequential administration of FEC followed by docetaxel in patients with node-positive, operable breast cancer.
Primary analysis of BCIRG 005 demonstrated no difference in OS or DFS when patients with node-positive breast cancer were treated with adjuvant TAC vs AC→T.
Results of NSABP B-30 demonstrated a benefit in OS (intent-to-treat; ITT) and DFS (ITT) with AC→T vs AT or TAC in patients with node-positive breast cancer.
Premenopausal patients who achieved amenorrhea had better survival.
Results from GEICAM 9805 demonstrated a significant DFS benefit in patients with high-risk, node-negative breast cancer treated with TAC compared to those treated with FAC.
Selected breast cancer subgroups (defined by age, HER2 status, intrinsic subtype, and biomarkers) must be evaluated to realize the maximum potential of chemotherapy.
USON 9735 and CALGB 49907 demonstrated that selected older patients do, indeed, derive benefit when treated with optimal chemotherapeutic regimens.
The importance of optimal agent, concurrent vs sequential therapy, and duration of therapy in HER2-positive disease was confirmed via presentation of results from several adjuvant trastuzumab breast cancer trials, including BCIRG 006, HERA, N9831, and FinHER.
Subset analyses from the CALGB 8541, CALGB 9344, and BCIRG 001 trials suggested that patients with HER2-negative/estrogen receptor (ER)–positive breast cancer did not derive benefit from chemotherapy.
Biomarkers are needed to define populations that will benefit the most for a given specific therapy. Ki-67 is predictive for docetaxel efficacy in HR-positive disease (PACS-01), and pAkt positivity may predict for taxane sensitivity in ER-negative disease (NSABP B-28).
The threshold for using adjuvant chemotherapy in addition to adjuvant endocrine treatment remains a controversial issue in 2010.
Two ongoing prospective clinical trials, TAILORx and MINDACT, will evaluate the role of chemotherapy in patients with an “intermediate” recurrence score and the safety of trusting the signature in discordant cases, respectively.
Luminal A and luminal B breast cancers respond differentially to chemotherapy; thus, it is important to distinguish these two subtypes.
Dr Piccart-Gebhart and colleagues developed a genomic grade index (GGI) based on 97 unique genes that are consistently differentially expressed between low-grade and high-grade breast tumors; indeed, data were presented demonstrating that GGI can define clinically distinct subtypes, including differentiation between low proliferative luminal A tumors from high proliferative luminal B tumors.
The results of several adjuvant aromatase inhibitor (AI) trials have been reported within the past year. The following important messages for clinical practice were presented to the audience:
Young women derive a large benefit from a late switching strategy, even if they have node-negative tumors.
Switching from letrozole to tamoxifen after 2 years does not appear to be detrimental within 6 years of follow-up.
The role of CYP2D6 in patients receiving tamoxifen remains unclear.
Most experts recommend against prescribing CYP2D6 inhibiting drugs for patients receiving tamoxifen, but there is no consensus regarding the role of CYP2D6 genotyping for intrinsic levels in patients for whom tamoxifen therapy is indicated.
Node-negative breast cancer does not automatically confer a good prognosis or define response to endocrine or chemotherapy.
New markers and tools should help to define the specific subgroups for more aggressive treatment.
The 10-year results of the Chemo-N0 trial demonstrated long-term prognostic impact of uPA/PAI-1 on OS, as well as the fact that patients deemed to be at low risk could be spared chemotherapy.
Routine histopathology complements the information provided by new genomic assays.
During the concluding panel discussion, led by Dr Piccart-Gebhart, it was clear that biology plays a central role in breast cancer treatment decision making. Emphasis was placed on initiating important clinical trials to validate new diagnostic tests, as well as the practical utility of genomic tests.
Memorable quotes from IBCC4
Wolfgang Eiermann, MD (University of Munich and Red Cross Women Hospital, Munich, Germany): “The conventional wisdom of today is individualized therapy.”
Sandra Swain, MD (Washington Cancer Institute, Washington, DC, United States): “We have reached the glass ceiling of the maximum potential of chemotherapy in unselected populations. To break through, we have to go to SELECTED subgroups!”
Martine Piccart-Gebhart, MD, PhD (Jules Bordet Institute, Brussels, Belgium): “It is becoming more and more important to make the distinction between luminal B and luminal A cancers for clinical practice and future research.”
John Crown, MD (St Vincent’s University Hospital, Dublin, Ireland): “Age is just a number.”
Frédérique Penault-Llorca, MD (Centre Jean Perrin, Clermont-Ferrand, France): “Can we clone Beppe Viale?”
This activity is supported by an educational grant from sanofi-aventis Groupe.
