Lung Cancer in Women

Abstract

Case Report

A 56-year-old Caucasian woman had a chief complaint of abdominal bloating. The symptoms had persisted for over 3 months without fever, chills, or weight loss. Attempts at dietary changes and over-the-counter (OTC) products did not decrease her symptoms. Results of complete blood count (CBC) and urine and stool studies along with a flat and upright abdominal film were negative. A screening colonoscopy had been negative at age 52. An abdominal computed tomography (CT) was performed. The results were negative for any pertinent finding related to her bloating, but incidentally noted was a 1.5-cm solitary pulmonary nodule in the left lower lobe. A chest x-ray 2 years earlier was reviewed and was negative for pulmonary nodule. A solitary pulmonary nodule (dynamic contrast enhancement) CT protocol was performed, indicating the nodule was worrisome for malignancy. A biopsy of the lesion revealed a malignant lung tumor. The patient is a nonsmoker.

The most likely histologic diagnosis for this tumor is:

A. Large cell carcinoma

B. Adenocarcinoma

C. Squamous cell carcinoma

D. Small cell lung carcinoma (SCLC)

E. Other

Discussion

From 1950 to 2001, women's death rates from lung cancer in the United States increased by 600%, and lung cancer has been the leading cause of cancer death in women since 1985. This disturbing trend has been described by the Surgeon General of the United States as a “full blown epidemic.”¹ Coincident with this rise in death rate was an increase in smoking rates among women. Smoking rates appeared to peak in 1965, when approximately one third of all women in the United States were smokers. Most recent reports suggest a significant decline in tobacco use, and it is estimated that today 18.3% of women are current cigarette smokers.² It was not until 2003–2007 that death rates from lung cancer were reported to decrease in women, suggesting that the peak of the epidemic has passed. This occurred more than a decade later than the drop in death rates in men.³ In spite of this small gain, lung cancer is still the leading cause of cancer death in women, with death rates surpassing those of breast and colon cancer combined.⁴

Lung cancer is classified into two main categories: small cell lung cancer (SCLC) and non-small cell lung carcinoma (NSCLC). SCLC accounts for about 15% of lung cancers in the United States overall and is more common in women than men, accounting for about 18% of lung cancer in women and 12% in men. NSCLC accounts for about 85% of lung cancer overall and is composed mainly of the histologic subtypes adenocarcinoma, squamous carcinoma, and large cell carcinoma. Adenocarcinoma is the most common histologic entity in the United States overall and in nonsmoking women, accounting for about 41.4% of NSCLC.⁵ Survival rates for lung cancer are better in nonsmokers, and women have a survival advantage across all tissue types and stages.⁵

The incidence of lung cancer in women who have never smoked is higher than in never-smoking men. The ratio of women to men in patients with lung cancer who have never smoked is approximately 3:1.⁶ A number of factors and risk factors have been explored, but the major cause of lung cancer in never smokers remains unexplained.⁷

An understanding of the role of estrogen in the development of lung cancer is evolving. The estrogen receptors (ERα and ERβ) are differentially expressed and may function in a tissue-specific manner. Estrogen receptor-mediated signaling can promote tumorigenesis, either through binding of estrogen or, independent of estrogen, through the expression of growth factors, such as epidermal growth factor receptor (EGFR).⁶ ERβ is found in normal lung tissue and in most NSCLC cell lines, whereas ERα is found in the uterus, kidney, and mammary tissue. In some women with adenocarcinoma, ERα can be overexpressed.⁸ Estrogens have been shown to stimulate proliferation of NSCLC cells in in vitro studies.⁷ In a post-hoc analysis by the Women's Health Initiative (WHI)⁵ a trend toward an increase in lung cancer was identified in women taking estrogen plus progesterone (E+P), and an increase in mortality from lung cancer was seen in the same group. This increase continued after cessation of therapy.⁹

Answer: B. Adenocarcinoma

In this case, the most likely answer is B. Adenocarcinoma of the lung is the most common histologic diagnosis for lung cancer in men and women. In this instance, the woman is also a nonsmoker, further increasing the likelihood that her cancer is an adenocarcinoma.⁵

Footnotes

Disclosure statement

The authors have no conflicts of interest to report.

References

www.cdc.gov/tobacco/data_statistics/sgr/2001/highlights/ataglance/index.htm Lung Cancer Epidemic, 2001 2011 June 25.

Lloyd-Jones

, Adams

, Brown

et al. Heart disease and stroke statistics—2010 update. A report from the American Heart Association. Circulation, 2010; 121:e46–e215.

Kohler

, Ward

, McCarthy

et al. Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Cancer Inst, 2011; 103:714–736.

American Cancer Society. Cancer facts and figures. Atlanta, GA: American Cancer Society, 2010.

Kligerman

, White

. Epidemiology of lung cancer in women: Risk factors, survival, and screening. AJR, 2010; 196:287–295.

Belani

, Marts

, Schiller

, Socinski

. Women and lung cancer: Epidemiology, tumor biology, and emerging trends in clinical research. Lung Cancer, 2007; 55:15–23.

Sun

, Schiller

, Gazdar

. Lung cancer in never smokers—A different disease. Nat Rev Cancer, 2007; 7:778–790.

Stabile

, Siegfried

. Estrogen receptor pathways in lung cancer. Curr Oncol Rep, 2004; 6:259–267.

Chlebowski

, Schwartz

, Wakelee

et al. Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): A post-hoc analysis of a randomised controlled trial. Lancet, 2009; 374:1243–1251.