HER2 Support Group Forums - Risk of Recurrent Disease in HER2-Positive Patients

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

<TABLE class=ccotable cellSpacing=0 cellPadding=0 width=500><THEAD align=left><TR><TH>Characteristic, %
</TH><TH>

Patients

</TH></TR></THEAD><TBODY><TR><TD>Age at diagnosis, yrs
</TD><TD></TD></TR><TR class=alternate><TD>

Younger than 50

</TD><TD>

16.2

</TD></TR><TR><TD>

50-59

</TD><TD>

20.6

</TD></TR><TR class=alternate><TD>

60-69

</TD><TD>

33.6

</TD></TR><TR><TD>

70 or older

</TD><TD>

29.4

</TD></TR><TR class=alternate><TD>

Unknown

</TD><TD>

0.2

</TD></TR><TR><TD>Tumor size, cm
</TD><TD></TD></TR><TR class=alternate><TD>

</TD><TD>

38.3

</TD></TR><TR><TD>

</TD><TD>

50.7

</TD></TR><TR class=alternate><TD>

</TD><TD>

5.5

</TD></TR><TR><TD>

Unknown

</TD><TD>

5.5

</TD></TR><TR class=alternate><TD>Grade
</TD><TD></TD></TR><TR><TD>

</TD><TD>

24.6

</TD></TR><TR class=alternate><TD>

</TD><TD>

48.0

</TD></TR><TR><TD>

</TD><TD>

24.6

</TD></TR><TR class=alternate><TD>

Unknown

</TD><TD>

2.7

</TD></TR><TR><TD>Number of lymph nodes
</TD><TD></TD></TR><TR class=alternate><TD>

</TD><TD>

48.0

</TD></TR><TR><TD>

</TD><TD>

26.6

</TD></TR><TR class=alternate><TD>

</TD><TD>

17,2

</TD></TR><TR><TD>

Unknown

</TD><TD>

8,2

</TD></TR><TR class=alternate><TD>PgR status
</TD><TD></TD></TR><TR><TD>

Positive

</TD><TD>

60.0

</TD></TR><TR class=alternate><TD>

Negative

</TD><TD>

36.6

</TD></TR><TR><TD>

Unknown

</TD><TD>

3.5

</TD></TR><TR class=alternate><TD>HER2 status
</TD><TD></TD></TR><TR><TD>

Positive

</TD><TD>

12.7

</TD></TR><TR class=alternate><TD>

Negative

</TD><TD>

86.1

</TD></TR><TR><TD>

Unknown

</TD><TD>

1.2

</TD></TR><TR class=alternate><TD>Radiotherapy
</TD><TD>

28.1

</TD></TR><TR><TD>Chemotherapy
</TD><TD>

25.4

</TD></TR></TBODY></TABLE>
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

<TABLE class=ccotable cellSpacing=0 cellPadding=0 width=500><THEAD align=left><TR><TH>Characteristic, %
</TH><TH>

DFS at 2.5 Yrs

</TH><TH>

DFS at 5.0 Yrs

</TH></TR></THEAD><TBODY><TR><TD>Overall
</TD><TD>

87.7 (86.1-89.3)

</TD><TD>

80.7 (78.7-82.7)

</TD></TR><TR class=alternate><TD>

PgR status

</TD><TD></TD><TD></TD></TR><TR><TD>

- Positive

</TD><TD>

91.7 (89.9-93.5)

</TD><TD>

86.0 (83.7-88.3)

</TD></TR><TR class=alternate><TD>

- Negative

</TD><TD>

80.7 (77.4-84.0)

</TD><TD>

71.8 (68.0-75.6)

</TD></TR><TR><TD>

HER2 status

</TD><TD></TD><TD></TD></TR><TR class=alternate><TD>

- Positive

</TD><TD>

74.5 (68.4-80.6)

</TD><TD>

70.5 (64.1-76.9)

</TD></TR><TR><TD>

- Negative

</TD><TD>

90.1 (88.5-91.7)

</TD><TD>

82.6 (80.5-84.7)

</TD></TR></TBODY></TABLE>

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.