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Tumor Discovery Pyrotinib and capecitabine in HER2-negative recurrence

HER2 status alterations post-neoadjuvant therapy. After (IHC) of the inner upper quadrant lesion demonstrated
1-3
chemotherapy, HER2-positive patients typically become estrogen receptor (ER) positivity (90%, moderate to strong)
HER2 negative, whereas the reverse is less frequent. A meta- (Figure 1D), progesterone receptor (PR) positivity (5%,
analysis reported a 21.3% conversion rate from HER2 weak to moderate), low HER2 expression (2+) (Figure 1E),
positive to negative and a 9.5% conversion rate from negative and Ki67 positivity (10%). IHC of the outer upper quadrant
to positive. Intratumoral HER2 heterogeneity, linked to lesion revealed low HER2 expression (2+) and positive
4
ambiguous expression and minor gene amplification, is results for ER (90%, moderate to strong), PR (90%, weak
5
associated with increased recurrence and metastasis and poor to moderate), and Ki67 (25%). HER2 amplification was
6
response to HER2-targeted therapy, impacting prognosis verified using fluorescence in situ hybridization (FISH)
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in metastatic cases. Despite the efficacy of combination (HER2/CEP17 ratio of 3.56) (Figure 1F). Consequently,
8
chemotherapy in treating HER2-positive cancer, residual she was diagnosed with hormone receptor (HR)- and
disease may cause loss of HER2 amplification, increasing the HER2-positive breast cancer (mcT2N0M0).
risk of recurrence and metastasis. 9-11 The patient received six cycles of neoadjuvant therapy,
Tyrosine kinase inhibitors (TKIs) have become pivotal which included docetaxel (75 mg/m ), carboplatin (area
2
in treating HER2-positive metastatic breast cancer. By under the curve 6), trastuzumab (initial dose, 8 mg;
inhibiting tyrosine kinases, enzymes that activate proteins subsequent doses, 6 mg), and pertuzumab (initial dose,
through signal transduction, TKIs can limit cancer cell 840 mg; subsequent doses, 420 mg). She underwent
growth and proliferation. HER2 is the target of several total mastectomy of the left breast and axillary lymph
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notable TKIs, including afatinib, lapatinib, neratinib, node dissection in May 2022 after showing a partial
tucatinib, and pyrotinib. In particular, pyrotinib, when response to neoadjuvant therapy, as determined by the
13
17
paired with capecitabine, significantly increases patient response evaluation criteria in solid tumors. Both the
survival. The PERMEATE trial revealed the efficacy of intraoperative frozen sections and post-operative skin
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pyrotinib and capecitabine against brain metastases in margins exhibited negative results (Figure 2A). The
HER2-positive cases. Pyrotinib also appears to be more surgical specimen revealed a moderately differentiated
15
potent than lapatinib in countering T-DM1 resistance. 16 invasive ductal adenocarcinoma of non-specific type
measuring 1.5 × 1.5 cm in the inner upper quadrant
This case report presents a breast cancer patient who (Figure 2B), with high-grade ductal carcinoma in situ,
transitioned from a HER2-positive status to HER2- comedo type, and no vascular or perineural invasion.
negative status following systemic anticancer therapy. One of the 10 dissected lymph nodes demonstrated
Upon experiencing recurrence with a HER2-negative metastases, including extranodal fibrous tissue. Of
lesion, the patient demonstrated a favorable response to the remaining nodes, one exhibited micrometastasis
the combination therapy of pyrotinib and capecitabine, (Figure 2C), and two contained isolated tumor cells
suggesting potential therapeutic benefits in such scenarios. (Figure 2D). The IHC results demonstrated low HER2
2. Case presentation expression (2+) (Figure 2E), PR negativity, and positive
results for ER (70%, weak to moderate) and Ki67 (3%),
In November 2021, a 38-year-old female noted a mass with a negative HER2 status on FISH (HER2/CEP17 ratio
in her left breast that persisted for 3 months. Physical of 1.65) (Figure 2F). Financial constraints prevented the
examination and imaging revealed two irregular, firm, patient from receiving T-DM1 therapy. Post-operative
mobile, non-tender lumps in the left breast: one located adjuvant radiotherapy included computer tomography-
1 cm from the nipple in the inner upper quadrant (5.0 × guided volumetric modulated arc therapy with 6MV-X
4.0 cm) and another 2 cm from the nipple in the outer external beam radiation, targeting the left chest wall and
upper quadrant (3.5 × 2.5 cm). In addition, a 2.0 × 1.0 cm supra/infra-clavicular areas. The planned target volume
firm, mobile, painless lymph node was identified in the was formed by expanding the clinical target volume by
left axilla. Breast cancer was confirmed through imaging 5 mm with a cumulative dose of 50 Gy in 25 fractions. The
modalities, such as mammography, magnetic resonance patient received goserelin and exemestane between May
imaging (MRI), and ultrasonography. Head MRI; neck, 2022 and February 2023. Sequential neratinib therapy was
chest, and abdominal computed tomography; and bone initiated but discontinued due to the onset of grade IV
scan did not reveal any distant metastases. A core biopsy diarrhea. The patient persisted with goserelin and
of two lesions in the left breast and axillary lymph node exemestane endocrine therapy. Two subsequent follow-up
revealed invasive ductal adenocarcinoma of non-specific visits revealed no abnormalities. The patient discovered a
type (Figures 1A and B) with two primary tumors and a chest wall lesion in November 2023 (Figure 3A). A biopsy
negative axillary node (Figure 1C). Immunohistochemistry of this lesion revealed invasive carcinoma (Figure 3B).

Volume 4 Issue 1 (2025) 114 doi: 10.36922/td.4093