A Lung Cancer Responding to Hormonal Therapy

Abstract

A 60-year-old woman presented with increasing dyspnoea and pain of several months duration. Radiology showed a 3 2.2-cm lung mass with mediastinal and subcarinal adenopathy and multiple vertebral metastases. A computed tomography-guided biopsy revealed a moderately differentiated adenocarcinoma. Immunohistochemistry showed positive staining for estrogen receptor (ER) (Figure 1a), thyroid transcription factor-1 (Figure 1b), and cytokeratin 7. The tumor was epidermal growth factor receptor (EGFR) positive as part of the entry criteria for a clinical trial. Staining was negative for progesterone receptor and cytokeratin 20, consistent with a lung primary. Her final diagnosis was of a T2N2M1 (stage IV) non-small cell lung cancer. Treatment was commenced with chemotherapy (cisplatin and vinorelbine) in combination with cetuximab and intravenous bisphosphonate therapy. Although she achieved a partial response that was maintained for 1 year, she progressed subsequently with her primary now measuring 4 3 cm (Figure 2a). Hormone replacement therapy, which she had commenced for menopausal symptoms, was stopped, and she was commenced on an aromatase inhibitor, exemestane. Within 3 weeks, her symptoms had improved, and repeat computed tomography scans 3 months later showed a decrease in the mass to 2.5 1.1 cm (Figure 2b), a partial response by Response Evaluation Criteria in Solid Tumors criteria, which was maintained for 6 months. Lung cancer is the leading cause of cancer death worldwide. The overall prevalence of smoking in any population has decreased in the past 20 years, but the relative decrease among women is much less. Women are more likely to be diagnosed with an adenocarcinoma than their male counterparts.1 Survival is better for women for all stages of lung cancer, even allowing for treatment differences.2 Genetic and molecular differences in lung cancers have been found between the sexes, includes differences in mutation rates of p53, EGFR, and k-RAS (Kirsten rat sarcoma) oncogene. The reasons for these differences in biologic behavior are not clear although it may be related to hormonal differences. Estrogens are implicated in the maturation, growth, and development of normal lung tissue. Hormone replacement therapy use is associated with a worse outcome in women with lung cancer, suggesting that estrogens may play a role in tumor progression.3 Two subtypes or ER have been described, ERand ER. ERreceptors are well characterized both in normal lung and malignant tumor samples, and immunohistochemistry positivity may be associated with an improved prognosis, particularly in males.4 Functional interactions between Departments of *Medical Oncology and †Histopathology, St James’s Hospital, Ireland. Disclosure: Ken J. O’Byrne has received Compensated Advisory Role, Honoraria, Research Funding, and other Remuneration with Pfizer, though not in relation to this case. Address for correspondence: Ian M. Collins, MB, MRCPI, HOPE Directorate, St James’s Hospital, Dublin 8, Ireland. E-mail: collins.ian@ gmail.com Copyright © 2010 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/10/0505-0749 FIGURE 1. a, Estrogen receptor staining positive and (b) TTF-1 staining positive. TTF, transcription factor.