Women's Health: Seeing lung cancer through the eyes of patients
Key Takeaways
- Lung cancer ranks among the top three diseases in the US nationwide.
- As with so many other diseases, lung cancer manifests in men and women differently regarding the type, symptoms, and prognosis of the disease.
As with so many diseases, lung cancer manifests in men and women differently in type, symptoms, and prognosis.
Women are more likely to develop adenocarcinoma, a type of non-small cell lung cancer. Adenocarcinoma begins in the glandular cells that line the lungs, is commonly located in the outer lung areas, and often grows more slowly than other forms, which can result in delays in the diagnosis2; delayed diagnosis may cause vague non-specific symptoms such as fatigue and back or chest pain.1
Men tend to develop squamous cell carcinoma, another form of non-small cell lung cancer typically found in the central airways of the lungs. This form is more closely linked to smoking and tends to produce earlier and more noticeable symptoms, such as coughing up blood, which makes diagnosis easier compared to adenocarcinoma.2. The squamous cell lung cancer in the main airways, in addition to coughing is also characterized by difficulty breathing.1
Women tend to have better survival rates, particularly those who were non-smokers, and may respond better to certain treatments,1 according to the investigators from Virginia Commonwealth University School of Medicine and Virginia State University, Richmond.
While lung cancer is not a sex-specific disease, it exhibits sex-specific trends, in that men are generally at a higher lifetime risk of developing lung cancer and have a higher mortality rate than women. Men and women also respond to treatment differently. “As lung cancer is a complex disease, this difference is likely a combination of environmental factors, such as environmental exposures, diet, and smoking status, with inherent biologic differences, such as the contribution of sex hormones and differences in immune responses,”1 May et al. commented.
Other factors in lung cancer
“Interestingly, adenocarcinoma is the most common form of lung cancer among non-smokers, and women, particularly younger women, are overrepresented in this group. Researchers suggest that hormonal differences, such as the presence of estrogen receptors in the lungs, may play a role in the development of adenocarcinoma in women. The slower progression of this cancer makes regular health screenings and monitoring critical for early diagnosis and better outcomes.”2
The high rate of adenocarcinomas reported in nonsmoking women suggests the possible existence of other etiologic factors in addition to smoking, which include gender-specific genetic alterations, passive smoking, age at onset of nicotine addiction, which is later in women than men, different nicotine metabolism in women, occupational exposure, diet, and chronic obstructive pulmonary disease.3
The Women’s Health Initiative investigated the genomic landscape of lung cancer in never-smokers and Moorthi et al.4 “found a significantly higher tumor mutational burden in smokers compared to never-smokers, and they also noted trends in mutations in the notorious oncogenes KRAS and EGFR; tumors from smokers had significantly more mutations in KRAS, while tumors from never-smokers had significantly more EGFR mutations.
May et al.1 noted the importance of widening the knowledge base about lung cancer. “Gaining a better understanding of the biologic reasons behind this sex difference could lead to better treatment and screening decisions in the clinic that take the biologic sex of the patient into consideration,” they said.
Current trend toward lung cancer development in younger women
Some culprits that have been identified include:
- Filtered cigarettes. More women started smoking years when filtered cigarettes were most common. These distribute tobacco smoke to the outer parts of the lungs, increasing the risk of adenocarcinoma lung cancer.2
- Genetics. Women may simply have different genetic risk factors for lung cancer than men, for instance, not being able to repair damaged DNA or possessing abnormal genes related to cancer development.2
- Less noticeable symptoms. Adenocarcinoma grows more slowly than other lung cancers and can be harder to detect. This can result in less prominent symptoms such as chest pain and coughing which can be mistaken for other conditions like asthma or bronchitis, making early detection less likely.2
The role of estrogen in lung cancer
Chakraborty and colleagues5 cited studies that examined the effects of hormone replacement therapy on survival. A study that retrospectively analyzed 429 women with lung cancer found that the “overall survival was significantly higher in women who had not undergone hormone replacement therapy compared with patients who received hormone replacement therapy (79 vs. 39 months; hazard ratio [HR]: 1.97). The survival benefit appeared to be more pronounced in women with a history of smoking.6
They also cited a post-hoc analysis of the Women’s Health Initiative trial, which was a randomized double-blind placebo-controlled trial of 16,608 postmenopausal women that compared combined hormone replacement therapy with placebo.5 Chlebowski et al. reported that more women died from lung cancer in the combined hormone therapy group than in the placebo group (HR: 1.71; 95% confidence interval [CI]: 1.16–2.52; P = 0.01). These effects were more pronounced in women who developed non-small-cell lung cancer (HR: 1.87; 95% CI: 1.22–2.88; P = 0.004).7 However, two other retrospective analyses did not find difference in lung cancer outcomes in women with lung cancer based on hormone replacement therapy.8,9
Impact of screening
A research letter by Bandi and colleagues from the American Cancer Society and published in JAMA,10 emphasized the importance of screening programs in the prevention of deaths from lung cancer, “Only approximately one in five eligible individuals in the US underwent lung cancer screening in 2024. Increasing current uptake to 100% could increase deaths prevented and life-years gained three-fold,” they commented.
Efforts to increase uptake include improving awareness of lung cancer screening recommendations and access to lung cancer screening facilities,11and targeting subgroups in whom lung cancer screening maximizes life-years gained.12
The eye and lung cancer
Soeroso et al.13 explained that most ocular metastases are asymptomatic. Blurred vision or changes in
Both non-small cell and small cell lung cancer are responsible for eye metastases.15 According to and co-authors, “Usually, pain is not a sign of metastatic cancer to the eye, except in cases that have an extensive intraocular tumor. The characteristic metastatic carcinoma to the choroid from the lung shows as a golden yellow to yellowish-white round to oval lesion.16 Metastatic carcinoma to the optic disk may appear as a swollen disk without a distinct mass or as a discohesive cellular infiltration of the superficial aspects of the optic disk.17 Metastatic carcinoma to the iris shows as a solid and amelanotic mass.18 Ciliary body metastatic carcinoma appears as diffuse or as multinodular mass, often associated with extensive retinal detachment and severe ocular pain, occurring sporadically. The precise mechanism for the pain in this sort of ocular metastatic carcinoma is not clear.18 Other metastatic carcinomas to the eye include infiltrative lesions of the neural retina18 and dispersed cells in the vitreous.19”
Other ocular changes include seeing spots, flashes of light, general loss of vision, a painful, red eye unresponsive to typical treatments, a new lump on the eyelid or a new mass on the iris, a partial or full retinal detachment, changes in eye position or movement, double vision or difficulty moving the eye.15
The double vision can be a symptom of tumors affecting the eye muscles or nerves; the changes in eye appearance, ie, a sunken or bulging eye might be a sign of a tumor in the orbit.Horner's syndrome can result from a tumor growing into nerves at the top of the lung and can result in a drooping eyelid and a smaller pupil on one side.20
Ophthalmologists typically have an important role in diagnosing and making differential diagnosis for the cases of lung cancer that has metastasized to the orbital. The most common symptoms and signs are abnormal eye position (65.22%), proptosis (63.04%), increased orbital pressure (54.35%), diplopia (54.35%), and limited eye motility (52.17%). These five symptoms are the most common clinical manifestations.21
Importantly, ophthalmologists are at the forefront in the diagnosis of metastatic ocular tumors, that may be the first indicators of lung cancer.
While oncologists treat the primary cancer, an ophthalmologist plays a crucial role in diagnosing and managing the ocular symptoms and providing palliative care to improve patient quality of life.
Finally, ophthalmologists can monitor for side effects of cancer treatments, such as those from immune checkpoint inhibitors, which can cause various eye problems.12
Illustrative cases
Case 1. A 32-year-old healthy woman presented with sudden-onset blindness of the right eye; she also reported occasional light flashes of light in her left eye for about 20 days. She had no history of smoking.
Examination showed non-painful eyes without redness and the ocular structures appeared normal. Closer examination showed a large, whitish-yellowish mass growing in the posterior segment. Fluid had also accumulated under her retina, causing a retinal detachment. detach. A smaller similar lesion was seen in her left.
The only test that was positive was a chest X-ray, and a whole-body scan showed a mass of cancerous tissue growing in the lower right lung. This tumor spread to multiple organs, including the choroid.
The treating physicians believed this case may have been the first example of a non-smoking woman of her age developing visual impairment as the first symptom of lung cancer.22 The physicians suspected a distinct subset of lung cancer that can spread without causing telltale symptoms of metastasis, they commented.
Case 2. A 59-year-old woman presented with a 3-week history of blurred vision in the left eye and no other or history of systemic complaints. Her best-corrected visual acuities were 6/36 in the right eye and 2/60 in the left. The anterior segment examination was normal bilaterally. Funduscopy showed a moderately elevated subretinal mass temporally in the midperipheral retina of the right eye and a moderately elevated subretinal mass inferiorly in the left eye associated with a macula-involving exudative retinal detachment.
Fundus findings supported a clinical suspicion of bilateral choroidal metastasis. She was evaluated by physicians and an oncology team to determine the site of primary malignancy. Two months after the initial presentation she developed a cough with hemoptysis and weight loss. She underwent radiotherapy followed by chemotherapy for palliation. She survived for 7 months after the initial presentation.23
Case 3. Soeroso and colleagues13 described the case of a 39-year-old woman who presented with a protruding sightless left eye, with pain and redness of 3-months duration, corneal opacity, conjunctiva bulbi, and chemosis; the pupil, iris, and lens could not be identified. The patient had a chronic cough but no history of trauma, systemic disease, familial cancer history, or previous ocular disorders. She had never smoked but was exposed to smoke from her husband’s smoking.
The physical examination showed delayed left hemithorax movement, decreased-to-diminished breath sounds of the mid-to-left lower lung zones, enlarged lymph nodes on the left side of the supraclavicular, and a lump in the left chest wall of the midclavicular line around the II-III ribs.
An orbital computed tomography (CT) scan showed a soft tissue tumor in the fronto-naso-superomedial area of the left orbital with suspected infiltration of the medialis rectus muscle, left bulbus oculi, lamina papyracea, and left frontal sinus wall, which caused proptosis, and a soft tissue tumor in the left temporal region with suspected infiltration in the left sphenoid wing that may still be a metastasis.
The chest x-ray showed a mass in the left perihilar and homogenous consolidation in the left lower lobe of the lung.
The chest CT scan showed an isodense mass with a relatively firm limit, lobulated with solid and half-solid components (±7 × 4 × 5 cm) in the 4th, 5th, and 8th segments of the left lung. Half of the mass edge was attached to the left pleural wall in which the pleural tail was stuck to the pericardium; the other half was attached to a large blood vessel. Multiple nodules (diameter, ±1.1 cm) were in the 4th, 5th, and 8th segment of the right lung. There was minimal pleural effusion in the left lung. There was also a ground glass opacity in both lungs, especially in the right lung. Bronchoscopy showed infiltrative masses covering LB 8 (segment anterior basal), and the biopsy result was adenocarcinoma. After fine-needle aspiration biopsy was conducted in the supraclavicular lymph nodes and chest wall, a similar result was found, namely metastatic adenocarcinoma. CT images showed no metastasis to the brain and bones.
Chemotherapy was offered to the patient. However, after one cycle of chemotherapy, the patient's condition deteriorated, and she eventually died, the authors reported.
Case 4. The authors reported a rare case of metastasis to the optic nerve from lung adenocarcinoma in a 59-year-old lethargic woman, a non-smoker, who presented with progressive visual blurring in the right eye for 1 month (visual acuity 6/18). She described headaches for the previous 2 weeks, left upper limb weakness for 1 day, and loss of appetite and weight for the past few months. No cough, fever, or shortness of breath were described. The bilateral eye vision was 6/18. Both anterior segments were unremarkable. Funduscopy showed normal optic nerves bilaterally.
A nervous system examination showed mild motor sensory impairment over the left upper and lower limbs and also impaired cranial nerves V and VII. Brain CT showed soft tissue lesions at the lateral aspect of the optic nerve and multiple recent cerebral infarcts. Brain and orbital magnetic resonance imaging showed a metastasis intraconal lesion at the right intraorbital segment of the optic nerve. Lung bronchoscopy diagnosed carcinoma of the left lung with distant metastasis. The patient generally deteriorated in less than 2 weeks and died 3 months after the initial presentation.24
Case 5. The investigators reported25 a 61-year-old woman who presented with a 2-week history of gradual deteriorating vision, morning headache, and nausea. She complained about a severe painless loss of vision in her right eye with blurred vision.
A clinical examination identified decreased breath sounds in the mid- to left-lower lung zones and instability on walking. An ophthalmic examination of the right eye showed decreasing visual acuity. Fundus examination showed an exudative retinal detachment in the right eye.
A magnetic resonance image showed a 16.5 × 10.7-mm right intraorbital mass of superolateral topography invading all of the ocular globe layers, and a second medial 8 × 3.7-mm right intraorbital mass. The posterior sclera and the periorbital fat were invaded, a with partial right retinal detachment.
These ocular lesions were associated with two left posterior parietal and left occipital necrotic-hemorrhagic lesions. Screening examinations were carried out as these lesions were suspected of being metastases. Chest computer tomography revealed a large mass on the left upper lung lobe and a small nodule on the left lower lobe suggestive of metastasis.
The biopsy results from bronchoscopy identified poorly differentiated non-small-cell lung carcinoma. Pathological results from the excision of both cerebral lesions were compatible with a primitive lung origin.25
The patient received systemic corticotherapy to reduce the inflammatory component of the exudative retinal detachment. After two courses, the cancer progressed and the patient was offered palliative care.
