Oncology Case Discussions


CASE 1: Infiltrating Ductal Carcinoma of Breast


Clinical History:

A 53 year-old healthy woman has a routine screening mammogram. Her menarche was at age 12. Her last menstrual period was 3 years ago. She used oral contraceptives for 20 years, and she has no children. A maternal aunt and a cousin had breast cancer at age 64 and 67 respectively. There is no other family history of cancer. The mammogram shows a spiculated 2 cm lesion with calcifications in the outer upper quadrant of the left breast. There are no lesions in the right breast. On your physical examination, you observe that she is mildly obese. The breasts are normal on palpation. She has no axillary masses, bony tenderness or other abnormalities. The neurological exam is normal. A chest xray shows no abnormalities. A CBC shows a Hgb of 13.7 g/dL, Hct 41.2%, MCV 90 fL, platelet count 288,000/microliter, and WBC count 5,760/microliter.

Findings:

The mammogram (images 1.1 and 1.2) reveals a mass above (to the right) of a radiopaque dot placed at the point of a palpable mass. The closer view reveals small white stippled microcalcifications in the region of the mass. Fine needle aspiration (image 1.3) shows a bloody background with some discohesive clusters of cells, features suggestive of a malignant process. The higher magnification view confirms the presence of malignant cells with high N/C ratio and hyperchromatic nuclei. The gross pathology of the lesion (image 1.4) is consistent with a carcinoma. Note how the tan mass is not circumscribed. Instead, it infiltrates into surrounding yellow fatty breast tissue. The dark green color to the surface of the specimen comes from "inking" the outside to mark the margins of the specimen, which will appear on microscopic slides and help determine if the lesion has been completely removed. Microscopically at low power the breast cancer has ill-defined nests and cords of cells that infiltrate through the stroma, with a prominent component of dense pink collagenous tissue--the so-called "desmoplasia" that gives breast cancers their hard, firm quality. At high magnification (image 1.5) there is an expanded duct is filled with malignant cells and rounded purplish microcalcifications. Around this duct are malignant cells infiltrating the stroma and forming smaller duct-like structures. Hence, this is an infiltrating ductal carcinoma. The cancer is positive for estrogen receptor (image 1.6) with dark staining of almost each nucleus. In contrast, HER2 staining is negative (image 1.7). The results of the flow cytometry (mage 1.8) reveal a large aneuploid peak and a high S phase, features that suggests a worse prognosis.

Questions:

  1. What is this woman's risk for having breast cancer? Is she likely to be a carrier of mutations in the BRCA1 or BRCA2 gene?

    2. Her risk is clearly increased over age-matched controls. However, as her relatives all had post menopausal breast cancer, she is unlikely to be a BRCA1 or BRCA2 carrier.

  2. If a screening mammogram had been normal, what preventive treatment might you offer her? What would be the risks and benefits of such therapy?

    3. She has some increased risk, but not enough to qualify for tamoxifen by the GAIL model. The guidelines for such drug usage are still provisional and additional ongoing trials will refine the choice of drug and indications for prevention. Risks: thrombosis, endometrial cancer. Benefits: reduction in breast cancer, heart disease, osteoporosis.

  3. What do you do now to make a diagnosis?

    4. A palpable mass would be biopsied. However, no mass is found on your physical examination. You can perform a mammogram, and if a suspicious lesion is found, it can be assessed by fine needle aspiration. The pathologist performing the FNA can determine at the bedside if adequate material is obtained for diagnosis.

  4. A mammographically-guided fine needle aspirate shows carcinoma. What staging tests would you order now?

    5. Staging tests vary according to symptoms and history. Typical tests would include a serum calcium and alkaline phosphatase (elevations would suggest bone metastases). Radiologic procedures could include a chest radiograph (to look for lung metastases), or if bone pain were present a bone scan. Neurologic problems might suggest performing an MRI to look for intracranial metastases. Other imaging studies would be indicated based upon your findings.

  5. The staging tests are unremarkable. What is her clinical stage? What do you do now?

    6. She is stage: T1c N0 M0 She should have surgery performed.

  6. A lumpectomy and axillary node dissection are performed. Pathological examination of the surgical specimen shows infiltrating ductal carcinoma, estrogen and progesterone receptor assays are positive. Staining for HER2/neu is negative. The specimen is 2.5 cm in its longest dimension, and the surgical margins are negative. Eighteen of eighteen axillary lymph nodes are negative for tumor. What is her final (pathological) stage?

    7. The stage remains the same as above. The clinical stage is often modified by subsequent surgical staging with additional findings (though this did not occur with this patient).

  7. Flow cytometry of the tumor cells shows a high aneuploid fraction and a high S-phase. How would this affect the prognosis?

    8. These are negative prognostic factors. Lack of aneuploidy and a low S-phase put her into a lower risk category. However, the exact role of flow cytometry findings in decision-making for breast cancer patients has not been finalized.

  8. What is her risk of developing recurrent disease? What should you do now?

    9. Many oncologists would observe this patient with follow up only. However, the poor risk flow cytometry pattern might persuade you to consider adjuvant tamoxifen for both prevention of recurrence and development of second primaries.

  9. What is the patient's risk for developing a clinical depression? Should she be referred to a mental health professional as part of an overall treatment program?

    10. Feelings of sadness and general emotional distress are a common reaction to diagnosis of cancer. Patients with greater amount of social support available tend to cope beter. Between 15 and 25% of breast cancer patients are diagnosed with a clinical depression. Of the patients that do develop a clinical depression, direct overlap of smoe symptoms of depression and cancer treatments (e.g., fatigue, general somatic compaints such as appetite and sleept disturbance). Individual and group psythotherapy focusing on cognitive and behavioral coping skills have been shown to be effective in improving the quality of life. Pain manaagement techniques and behavioral techniques targeting nausea and coping strategies for painful procedures is also effective. For patients with more severe levels of depression, antidepressant medication may be used.