De Novo Oligometastatic HER2+ Breast Cancer

Presentation

A 38-year-old female patient who is 3 months pregnant reports to her obstetrician that she self-palpated a right breast mass. The OB sends the patient for a fine needle aspiration (FNA) and breast ultrasound, which notes a benign 1.2 x 1.0 x 1.4 cm simple cyst in the right outer central breast at 9 o'clock, 12 cm from the nipple.

Six months later, the patient gives birth and begins breastfeeding. At her 6-week postpartum checkup, the OB notes that she has breast asymmetry, and the patient reports having noticed right breast redness starting 1 month before the birth.

Workup and Diagnosis

The patient stops breastfeeding at this time and undergoes a mammogram, which reveals diffuse edema and skin thickening in right breast, global asymmetry in the outer right breast, and microcalcifications in the outer central breast spanning an area of 8.4 cm, as well as multiple prominent right axillary lymph nodes (LNs). Breast ultrasound shows suspicious right breast masses in the upper outer quadrant that are hypoechoic and irregular, with the largest measuring 4.8 x 3.8 x 4.2 cm. Also found were multiple abnormal right axillary LNs (levels I, II, and Rotter's). Biopsy of the dominant breast mass and one of the nodes reveals adenocarcinoma that is ER-/PR-/HER2+ (IHC 3+, FISH positive).

Breast MRI notes right breast edema and skin thickening (possible lymphatic obstruction vs. inflammatory breast carcinoma), >9-cm disease in the right outer breast with extension to lower central breast, multiple abnormal right axillary LNs (levels I, II, III), 2 prominent right intramammary LNs, as well as nonspecific mildly hyperintense focus in the right hepatic lobe. PET/CT notes two enhancing foci in the brain as well as enlarged cervical LN, and 2 liver lesions measuring 2 x 1.5 cm and 1.1 x 1.4 cm, one of which is FDG avid. Abdominal MRI shows a 1-cm lesion suspicious for metastases and a separate lesion that appears to be a hemangioma. Brain MRI does not show brain metastases. Liver FNA reveals metastatic breast cancer that is ER-/PR-/HER2+ (IHC 3+; FISH not performed).

Treatment

The patient is started on weekly paclitaxel 80 mg/m² x 12 weeks with concurrent trastuzumab and pertuzumab every 3 weeks. This is followed by doxorubicin and cyclophosphamide every 3 weeks x 4 cycles, per NCCN Guidelines.¹

After the patient completes initial treatment, imaging is repeated to determine response. PET/CT shows residual right breast thickening, stable right axillary node, and decreased size of the previously biopsied liver metastasis with resolved FDG avidity, as well as a stable benign hemangioma. Abdominal MRI shows complete resolution of the liver metastasis and stable hemangioma. Breast MRI revealed diffuse non-mass enhancement in the entire lower right breast, which extends cranially to the level of the nipple to involve the central breast.

One month after completing chemotherapy, the patient undergoes bilateral mastectomy and right axillary LN dissection, which shows no residual disease in right breast or nodes.

She then completes radiation to the right breast (5000 cGy in 25 fractions). She continues trastuzumab and pertuzumab every 3 weeks.

Follow-Up

For the next 3 years, follow-up PET/CTs continue to show no evidence of disease. She does not report experiencing diarrhea or rash, which are the most common side effects seen among patients receiving pertuzumab and trastuzumab.² Her echocardiograms are followed, and her ejection fraction remains stable in the normal range.

Discussion

Our patient is considered to have metastatic disease but with only one site of distant disease. The choice to treat her with curative intent is not uncommon. Evidence shows that patients with oligometastatic disease can have improved survival after receiving therapy with curative intent.³

This patient’s treatment started in 2015. Had she presented today, how might her treatment have been different? Would we consider docetaxel, carboplatin, trastuzumab, and pertuzumab every 3 weeks x 6 cycles instead?^4,5

Let’s now imagine that this patient had multiple liver lesions. How would this have changed our approach? Based on the CLEOPATRA trial, we could have offered her docetaxel, trastuzumab, and pertuzumab every 3 weeks as her initial treatment.² After the first 4 cycles, a PET/CT shows partial response in the liver and breast. She then completes 4 more cycles and undergoes PET/CT, which reveals complete metabolic response in the breast and liver. Docetaxel is stopped and trastuzumab and pertuzumab are continued, with now 7 years of scans showing no evidence of disease. After a few years, would you consider breast imaging annually? In my practice, I will order a mammogram annually to assess for local recurrence or new primary cancer because CT and PET/CT often don’t pick up subtle disease in the breast. Would you ever consider this patient cured and stop trastuzumab and pertuzumab? In my practice, I have seen some providers choose to stop trastuzumab and pertuzumab after 10 years of no evidence of disease, while others continue indefinitely.

References

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 4.2022. June 21, 2022. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf Accessed January 8, 2023.
2. Swain SM, Miles D, Kim S-B, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-30.
3. Harris E, Mitchel B, Kell MR. Meta-analysis to determine if surgical resection of the primary tumour in the setting of stage IV breast cancer impacts on survival. Ann Surg Oncol. 2013;20:2828-34.
4. Schneeweiss A, Chia S, Hickish T, et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018;89:27-35.
5. Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24:2278-84.