EGFR-mutant NSCLC may be risk factor for primary breast cancer

Liz Meszaros, MDLinx | March 06, 2019

Patients with EGFR-mutant non-small cell lung cancer (NSCLC) may be more likely to develop second primary breast cancers compared with those without this mutation, according to results of a recent study published in Oncology Research and Treatment.


Researchers have discovered a significant difference in the probability of having both breast cancer and lung cancer between NSCLC patients with and without EGFR mutations.

Although the incidence of patients with cancer who have developed a second primary malignancy (SPM) is rather low—8.1% according to Surveillance, Epidemiology, and End Results (SEER) data—the lung is the most common site.

With the recent uptick in the number of patients diagnosed with an SPM, researchers led by Teresa Moran, MD, Medical Oncology, Catalan Institute of Oncology, Badalona, Hospital Germans Trias i Pujol, Universitat Autòmoma de Barcelona, Badalona, Spain, noted that “There is a clear need for a better understanding of the molecular, environmental, and clinical factors underlying SPM development.”

After reviewing the factors historically linked to a higher risk of developing lung cancer, including smoking and genetic factors, these researchers noted the role of estrogens in cancer development as well.

“All our patients were never-smokers, and only [one] patient had Li Fraumeni syndrome which carries the risk of developing [lung cancer] and other tumors. The rest of our patients had no genetic history related to a higher risk of cancer. Estrogens are known to play a role in carcinogenesis. Postmenopausal patients who received hormone replacement therapy (HRT) for more than 10 years had a higher risk of developing [lung cancer]. Nevertheless, the relationship between estrogen and [lung cancer] is unclear and has not been examined in patients with EGFR-mutant NSCLC,” they wrote.

To test their hypothesis that patients with EGFR-mutant lung cancer may have a higher incidence of primary breast cancer compared with patients with EGFR-wild type (WT) lung cancer, Dr. Moran and her fellow researchers conducted this single-center, retrospective study in 356 women with lung cancer and a previous or simultaneous history of primary breast cancer treated at the Lung Cancer Unit of the Catalan Institute of Oncology, Hospital Germans Trias i Pujol.

They gathered data on patients’ clinical and molecular characteristics, as well as on treatment, follow-up, and EGFR mutation status, which was evaluated using a DNA sample kit. Dr. Moran and colleagues also used fluorescent in situ hybridization to assess HER2 amplification in all patients, and immunohistochemistry to determine their hormone receptor status (estrogen, progesterone, and androgen receptors).

In all, 17.7% of 62 patients with EGFR mutations had breast cancer compared with only 1.02% of the 294 patients with EGFR-WT (P < 0.001). In 81.8% of patients with both cancers, tumors in both locations were metachronous. In these patients, lung cancer was diagnosed a median of 9 years (range: 3-22 years) after their diagnosis of breast cancer.

A full 72.8% of breast cancers were diagnosed as stage I-II, while 18.2% were diagnosed as ductal carcinoma in situ. Most lung cancers were also diagnosed as stage I-II, and del19 was the most common EGFR mutation (72.7%).

Most of the six patients with breast cancer who were treated with radiotherapy (83.3%) developed lung cancer in an area that was located within the radiation field. Among patients with lung cancer who required treatment, 63.6% were treated first-line with a tyrosine kinase inhibitor (TKI).

In the 11 patients with both EGFR-mutant lung cancer and breast cancer, overall survival (OS) as calculated from time of lung cancer diagnosis was 91.3 months, and from the time of breast cancer diagnosis, 303.37 months. Median progression-free survival in patients treated with first-line TKIs for NSCLC was 9.1 months, and median OS, 40.5 months.

In all, 90.9% of patients had no breast cancer recurrence. At the time of analysis, 6 of these 11 patients had died due to lung cancer. Of the five remaining patients, three were disease-free, one was on treatment with an EGFR-TKI, and one continued treatment for recurrent breast cancer plus an EGFR-TKI for metastatic breast cancer.

Researchers detected no EGFR mutations in breast cancer tissue, and no HER2 expression in lung cancer tissue samples.

“In conclusion, although our findings must clearly be interpreted with caution due to the small sample size, we have found a significant difference between NSCLC patients with and without EGFR mutations in the probability of having both [breast cancer] and [lung cancer]. This difference may be partially attributable to prior exposure to hormone therapy or radiotherapy, but further investigation is warranted to elucidate the potential underlying molecular link between [breast cancer] and EGFR-mutant NSCLC,” concluded Dr. Moran and colleagues.