- •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.
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.
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).
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.
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.
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).
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.
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Accepted: March 3, 2023
Received in revised form: February 21, 2023
Received: November 17, 2022
Publication stageIn Press Journal Pre-Proof
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