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ABSTRACT

A 45 year old female was diagnosed to have invasive ductal carcinoma of left breast. Following mastectomy and adjuvant chemotherapy and radiation therapy she progressed with brain metastases. After palliative chemotherapy based on lapatinib and capecitabine the brain metastases resolved completely. We report a patient with brain metastases from HER2 positive breast cancer that was successfully treated with radiation and a combination of lapatinib and capecitabine.

Complete Response of Brain Metastases in HER2 Positive Breast Cancer after Treatment with

Lapatinib and CapecitabineMohd Shafi Moona, Arwa Nabhan, Farah Waqar.

Department of Medical Oncology, King Abdullah Medical City & Oncology Center, Jeddah, Kingdom of Saudi Arabia.

Key Words: Breast cancer, brain metastases, HER2 positive, lapatinib.

INTRODUCTION

Patients with HER-positive breast cancer who have been treated with trastuzumab are at greater risk for developing brain metastasis with the incidence ranging from 25% to 36%1-4. Treatment is based on whole brain radiotherapy. Few systemic options are available. HER2 over-expression is associated with poor disease free and overall survival in breast cancer patients and with a tendency for visceral site metastases5. One-third of patients with HER2-positive metastatic breast cancer who are being treated with trastuzumab develop brain metastases which occur within 2 years6,7. Trastuzumab is a highly selective monoclonal antibody which targets the extracellular domain of the HER2 receptor and does not fully cross the blood brain barrier. Although several studies of treatments for patients with metastatic breast cancer have indicated that lapatinib provides favorable response, only a few studies have shown that lapatinib achieved complete response (CR) in patients with brain metastases8,9.

Corresponding Author: Mohd Shafi Moona, Department of Medical Oncology, King Abdullah Medical City & Oncology Center, Jeddah, Kingdom of Saudi Arabia.Phone: 00966-534657147, E-mail: drshafimoona@yahoo.co.in

132Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 13, No. 3, July 2014

CASE REPORT

45 year old female presented in March 2007 with left breast lump measuring 6x6 cm with nipple retraction and skin fixation. Tru-cut biopsy was taken and histopathology was invasive ductal carcinoma, grade 11, ER+ve, PR +ve and HER2 +ve. Metastatic work up with CT scan chest, abdomen and isotope bone scan was done which was normal. The disease was staged 111B (T4N1M0). Received 2 cycles of neo-adjuvant chemotherapy based on TEC regimen. On clinical examination the breast lump decreased in size measuring 2x2 cm and complete remission of left axillary lymph node. Received two more cycles of same chemotherapy. Breast conservative surgery and axillary clearance was done in May 2007 and on histopathological examination there was no evidence of residual tumor. Six lymph nodes were removed and all were free. Patient received 4 cycles of adjuvant

chemotherapy based on TEC regimen till October 2007. Received adjuvant radiation therapy till December 2007. In December 2007 started Trastuzumab and adjuvant hormonal treatment based on Femara, Zoladex and 6 monthly zoledronic acid. In January 2008 patient developed small nodule at lumpectomy scar. Excision was done and on histopathological examination there were residual tumor cells. In February 2008 Mastectomy was done and on histopathological examination there was no evidence of disease. CT scan chest and abdomen was done which was normal. Patient continued hormonal treatment and received 12 doses of trastuzumab. In January 2009 patient presented with headache. CT brain was done showed brain metastases (fig1, 2). Received palliative WBRT till 31stJan 2009. Palliative chemotherapy was started based on Lapatinib and capecitabine (LC). CT scan done after 4 cycles of chemotherapy showed complete response of brain metastases (fig 3, 4). Patient

(fig 1)

(fig 3)

(fig 2)

(fig 4)

Mohd Shafi Moona

133Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 13, No. 3, July 2014

continued on chemotherapy and received 13 cycles till May 2010. Re-evaluation with CT chest, abdomen and brain was done which was normal. So chemotherapy was stopped and patient was kept on follow up. Re-evaluation done in Jan 2013 showed new enhanced focal lesion in left cerebrellar hemisphere and tiny sub-pleural nodules measuring 3 and 4mm at posterior aspect of right upper and lower lung lobes and small left lung nodule posteriorly. So palliative chemotherapy based on lapatinib and capecitabine was resumed as patient received LC for 17 months and remained in complete remission for 32 months after stopping chemotherapy. Received 11 cycles of lapatinib and capecitabine till September 2013. Re-evaluation with CT scan chest, abdomen and brain was done which was stationary. So chemotherapy was stopped and hormonal treatment based on tamoxifen started.

DISCUSSION

Trastuzumab, a monoclonal antibody against the extracellular domain of the HER2 receptor10, has markedly improved the survival of HER2 positive breast cancer patients11. However, CNS disease remains a challenge, since HER2 positive breast cancer patients are more prone to brain metastasis, whether or not previously exposed to trastuzumab. Trastuzumab does not cross blood brain barrier. Trastuzumab has limited penetration through the blood brain barrier. The ratio of trastuzumab level in serum to cerebrospinal fluid is found to be 430:1, thus making the brain vulnerable for the development of metastases5. Lapatinib offers a treatment option for HER2 positive patients who progress on trastuzumab. Lapatinib is a small molecule inhibitor of both EGFR and HER2. Lapatinib penetrates the blood brain barrier, whereas trastuzumab, with a high molecular mass, does not efficiently cross the blood brain barrier, which accounts for its poor efficacy against brain metastases. Overexpression of HER2 indicates poor prognostic factor for overall and disease-free survival, and it is a risk factor for the development of brain metastases.

Gabos et al. followed up 363 HER2-negative and 301 HER2-positive breast cancer patients during 3.9 years. Brain metastasis was found to be 9% in HER2-positive cases and 1.9% in those with HER2 negative cases12. Ro et al. administered LC to patients with HER2 positive breast cancer metastasizing to the brain. CR was achieved in 2of 47 patients who received WBRT8. Abboud et al. reported one patient with brain metastases from HER2 positive breast cancer who achieved CR after LC9. One patient with brain metastases from breast cancer in HER2

positive breast cancer who achieved complete response after LC was reported by Mariko Kiruchi et, al13. Lin et al. have also conducted several trials on patients with HER2 positive breast cancer metastasizing to brain; CR was not achieved in any patient14,15. Because there have been only few cases reported in the literature brain metastases from HER2 positive breast cancer who had complete response after treatment with LC. The case we are reporting provides an additional support for the efficacy of LC and suggests that LC treatment may have a significant efficacy for brain metastases from HER2 positive breast cancer.

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Mohd Shafi Moona