Highlights
- •After NAT, the majority of ER-low positive tumors had the change of ER status.
- •After NAT, the change in HER2 status was mainly the conversion from HER2-zero to HER2-low.
- •After NAT, the largest proportion of HER2-low patients had decreased Ki67 index.
- •ER conversion had a positive correlation with pre-treatment ER status.
- •There was a positive correlation between HER2 conversion and HER2-targeted therapy.
Abstract
Background
Few studies have focused on converting ER-low-positive and HER2-low status following
neoadjuvant therapy (NAT). We aimed to assess the evolution in ER and HER2 status
after NAT in breast cancer patients.
Patients and Methods
Our study included 481 patients with residual invasive breast cancer after NAT. ER
and HER2 status were assessed in the primary tumor and residual disease, and associations
between ER and HER2 conversion and clinicopathological factors were explored.
Results
In primary tumors, 305 (63.4%) cases were ER-positive (including 36 cases of ER-low-positive),
176 (36.6%) were ER-negative. In residual disease, ER status changed in 76 (15.8%)
cases, of which 69 cases switched from positive to negative. ER-low-positive tumors
(31/36) were the most likely to change. In primary tumors, 140 (29.1%) tumors were
HER2-positive, and 341 (70.9%) were HER2-negative (including 209 cases of HER2-low
and 132 cases of HER2-zero). In residual disease, 25 (5.2%) cases had HER2 conversion
between positive and negative. Considering HER2-low status, 113 (23.5%) cases had
HER2 conversion, mostly driven by cases switching either to or from HER2-low. ER conversion
had a positive correlation with pretreatment ER status (R=0.25; p=0.00). There was a positive correlation between HER2 conversion and HER2-targeted
therapy (R=0.18; p=0.00).
Conclusion
Conversion of ER and HER2 status was observed in some breast cancer patients after
NAT. Both ER-low-positive and HER2-low tumors showed high instability from the primary
tumor to residual disease. ER and HER2 status should be retested in residual disease
for further treatment decisions, especially in ER-low-positive and HER2-low breast
cancer.
Background
ER and HER2 status may change after neoadjuvant therapy (NAT) in breast cancers. There
have been variable discordance rates of ER and HER2 status pre- and post-NAT in previous
studies. Few studies have focused on conversion of ER-low and HER-low expression status
after NAT. We aimed to assess the evolution in ER and HER2 status after neoadjuvant
therapy in breast cancers.
Patients and Methods
Our study included 481 breast cancer patients with residual invasive cancer after
NAT. ER and HER2 status were assessed in primary tumour and residual disease, and
associations between ER and HER2 conversion with clinicopathological factors were
explored.
Results
In primary tumours, 305 (63.4%) cases were ER positive (including 36 cases of ER-low-positive),
176 (36.6%) were ER negative. In residual diseases, ER status changed in 76 (15.8%)
cases, in which 69 cases switched from positive to negative. 81.1% (31/36) ER-low-positive
tumours had inconsistent status after NAT, in which 23 cases became negative. ER-low-positive
group (OR 87.77, 95% CI 23.82–323.44, p< 0.00) was the most prone to change. In primary
tumours, 140 (29.1%) tumours were HER2 positive, 341 (70.9%) were HER2 negative. In
HER2 negative tumors, 209 (43.5%) were HER2-low and 132 (27.4%) were HER2-zero. In
residual diseases, 25 (5.2%) cases had HER2 conversion between positive and negative
status (K=0.87 p=0.00). However, considering HER2-low status, 113 (23.5%) cases had HER2 conversion
(K=0.64 p=0.00), mostly driven by cases switching either to or from HER2-low. ER conversion
had a positive correlation with pre-treatment ER (R=0.25; p=0.00) status. There was
a positive correlation between HER2 conversion and HER2-targeted therapy (R=0.18; p=0.00).
Conclusion
Conversion of ER and HER2 status was observed in some breast cancers after NAT. ER-low-positive
and HER2-low tumours both showed high instability from primary tumor to residual disease
after NAT. ER and HER2 status should be retested in residual disease for further treatment
decision, especially in ER-low and HER2-low expression breast cancers.
Key words
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Article info
Publication history
Accepted:
March 3,
2023
Received in revised form:
February 21,
2023
Received:
November 17,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
