[Barbara2]

Here is the capsule summary of the data from this study:

Capsule Summary

CCO Independent Conference Coverage of the 2009 Annual Meeting of the AACR-CTRC San Antonio Breast Cancer Symposium*

*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.


HER2 Positivity a Risk Factor for Recurrence in ER-Positive Early-Stage Breast Cancer

Posting Date: December 15, 2009

• Analysis of prognostic factors in retrospective cohort dataset

Summary of Key Conclusions

• HER2, estrogen receptor (ER)–positive patients with early-stage breast cancer at significantly increased risk of recurrent disease within 2.5 years after diagnosis
  • Peak in annual recurrence rate at 2 years in HER2-positive group
• AIs reduce the risk of recurrence in HER2-positive patients
  • Trastuzumab should be considered for ER-positive, HER2-positive patients given that inhibition of growth factor signaling may increase response to endocrine therapy

Background

• AIs provide survival benefit in ER-positive early-stage breast cancer and reduce risk of recurrence
  • Optimal timing for initiation of AI therapy in relation to tamoxifen therapy not well defined
  • Identification of prognostic markers would be helpful in selection of patients for treatment with AIs
• Current study sought to determine whether progesterone receptor (PgR) status or HER2 status predictive for recurrence in ER-positive early breast cancer

Summary of Study Design

• Analysis of ER, PgR, and HER2 expression in retrospective cohort of women with symptomatic early-stage breast cancer diagnosed between 1980 and 2002 and treated with adjuvant tamoxifen
• Definition of recurrence
  • Invasive malignancy on histopathology at any site or
  • High index of suspicion upon radiologic investigation
• Primary study endpoint
  • Kaplan-Meier analysis of DFS: 2.5 years and 5.0 years
  • Time-dependent Cox regression analysis assessed using term ≤ 2.5 years
• HR for recurrence rate per year by panechnikov smoothing function; bandwidth of 6 months
• Multivariate time-dependent analysis
  • Adjusted for HER2 status, tumor size, grade, nodal status, PgR status, and HER2 status associated with DFS at time from diagnosis

Baseline Characteristics

• Patient and disease characteristics at baseline

Characteristic, %	Patients
Age at diagnosis, yrs
Younger than 50	16.2
50-59	20.6
60-69	33.6
70 or older	29.4
Unknown	0.2
Tumor size, cm
< 2	38.3
2-5	50.7
> 5	5.5
Unknown	5.5
Grade
I	24.6
II	48.0
III	24.6
Unknown	2.7
Number of lymph nodes
0	48.0
1-3	26.6
> 3	17,2
Unknown	8,2
PgR status
Positive	60.0
Negative	36.6
Unknown	3.5
HER2 status
Positive	12.7
Negative	86.1
Unknown	1.2
Radiotherapy	28.1
Chemotherapy	25.4

Main Findings

• Tumors confirmed as ER positive (n = 402)
  • Median follow-up: 6.1 years
  • Median age of cohort: 63 years
  • PgR positive, 60%
  • HER2 positive, 12.7%
• HER2-positive status associated with lower DFS rates at 2.5 and 5.0 years

Characteristic, %	DFS at 2.5 Yrs	DFS at 5.0 Yrs
Overall	87.7 (86.1-89.3)	80.7 (78.7-82.7)
PgR status
Positive	91.7 (89.9-93.5)	86.0 (83.7-88.3)
Negative	80.7 (77.4-84.0)	71.8 (68.0-75.6)
HER2 status
Positive	74.5 (68.4-80.6)	70.5 (64.1-76.9)
Negative	90.1 (88.5-91.7)	82.6 (80.5-84.7)

• Univariate analysis of factors significantly associated with DFS
  • Tumor size: P < .001
  • Grade: P < .001
  • Nodal status: P < .001
  • PgR status: P = .002
• Multivariate time-dependent analysis between HER2 status and time dependant term
  • ≤ 2.5 years, HR: 2.54 (95% CI: 1.21-5.32)
  • > 2.5 years, HR: 0.33 (95% CI: 0.10-1.11; P = .004)
• Peak in annual recurrence rate at 2 years in HER2-positive group

Reference

Mansell J, Tovey S, Angerson WJ, Wilson CR, Doughty JC. The tnfluence of HER2 status on the recurrence pattern in oestrogen receptor positive (ER+) early breast cancer (EBC). Program and abstracts of the 32nd Annual San Antonio Breast Cancer Symposium; December 9-13, 2009; San Antonio, Texas. Abstract 4045.