Early screening, adjuvant and sequential systemic treatment, and hormonal therapy have benefits in treatment of breast cancer. Management of non-small-cell lung cancer (NSCLC) is progressing and will hopefully follow in the same footsteps as that of breast cancer. Only recently have clinical trials established adjuvant treatment as the standard of care in lung cancer. A growing number of effective cytotoxic and targeted agents have resulted in increased survival when used as sequential treatment in both breast cancer and NSCLC. The interaction between oestrogen receptors (ER) in the lung and epidermal growth factor receptor (EGFR) suggests a potential role for endocrine manipulation in the treatment of NSCLC. This complex interaction involves several types of ER receptors and different signalling pathways. Interactions between tobacco and oestrogen confound the effects of exogenous oestrogens on risk of lung cancer, but not on that of breast cancer. The optimum application of hormonal manipulation to prevent or treat lung cancer will depend on a more-complete understanding of lung-specific ER signalling. Early trials have assessed the interaction between the ER and EGFR signalling.