Breast Cancer – Diagnosis, Symptoms, and Treatment

What is Breast Cancer?

Breast cancer is one of the most common cancers in women and a rare cancer in men. It develops from cells that make up the milk ducts and glands in the breast tissue.  There are many genes that are known to cause breast cancer and this disease is known to have a strong genetic link, frequently appearing in multiple close relatives.  Patients may have a breast mass, enlarged lymph nodes in the armpits, breast pain, dimpling of the skin, or nipple abnormalities.  Patients that have yet to develop any masses or symptoms may also be detected by routine breast cancer screening with a mammogram.

Patients with advanced disease have a poor prognosis, but screening mammography and early detection of breast cancer have resulted in a significant increase in survival rate.  Despite this, breast cancer is still a leading cause of cancer death and overall mortality in the United States.

What Causes Breast Cancer?

As with all cancers, breast cancer results from a combination of genetic and environmental factors. Some individuals have a combination of genes that slightly increases their risk for breast cancer while others have specific genes that make breast cancer a near certainty. The environmental factors that lead to breast cancer are less clear. Exactly what substances in our diets and living spaces contribute to cancer is an area of ongoing research. 

Some of the major risk factors for breast cancer include:

• Advanced age
• Female gender
• Caucasian race
• Obesity in postmenopausal women
• Exposure to high estrogen levels during early menarche or late menopause
• Reproductive factors - late first pregnancy, lack of breastfeeding, and never having been pregnant (nulliparity)
• Alcohol consumption
• Cigarette smoking

Many of the lifestyle factors that lead to overall better health such as; regular exercise and a diet rich in fruits, vegetables, and lean meat (e.g., fish) can lower your risk for any cancer, including breast cancer.

How Common is Breast Cancer?

Breast cancer is extremely common in theUnited States, with approximately 250,000 cases annually. This rate has been decreasing as research has revealed some of the genes and medications, such as hormone replacement therapy, that are now known to increase the risk of breast cancer. The survival rate of those with cancer is also increasing as early detection and advanced surgical methods increase the likelihood of a life-long cure. Despite this decrease in incidence breast cancer still results in over 40,000 deaths per year. 

Signs and Symptoms

Breast cancer is commonly asymptomatic and is detected on routine screenings with mammography or during self breast exams. Occasionally, patients will develop signs and symptoms that are concerning for potential cancer, the most common being:

• Breast mass
• Breast discomfort or pain
• Axillary (armpit) mass
• Nipple retraction or abnormalities
• Dimpling of the skin “peau d’orange” – due to skin swelling

Breast masses are most frequently located in the upper-outer quadrant of the breast.  They are often firm, irregular, and do not move during palpation of the breast tissue.  In more severe cases the lymph nodes in the armpit (axilla) may be affected as the cancer cells migrate, or metastasize, out of the breast tissue to other areas in the body.  Other lymph nodes in the chest, head, and neck may also become involved in severe cases. By the time masses form in areas other than the breast more severe symptoms that affect the entire body such as fatigue and weight loss generally develop.

Patients with distant metastatic disease, which refers to the spread of cancer cells to the brain, lungs, and bones, may develop bone pain in the back or leg, liver abnormalities, and lung symptoms (e.g., cough, difficulty breathing).

Diagnosis

Breast cancer may be suspected based on your family history, breast exam, the detection of a mass, or the findings on a mammogram. But the diagnosis is formally made with a biopsy.

Asymptomatic women who have a breast mass on a routine screening mammogram typically undergo a needle breast biopsy guided by x-ray or ultrasound.  Those that have a palpable breast mass typically receive fine-needle aspiration or core needle biopsy of the lesion.  Individuals with quickly progressive lesions that are tender with signs of thickening and hardening of the skin require a full-thickness skin biopsy, where some or all of the offending mass is removed and evaluated.

The tissue that is removed during the biopsy is analyzed first to determine if is cancerous, if that cancer is malignant, meaning it is a type that can spread, and if it contains any special receptors. 

Breast cancer cells may be coated in a large number of special receptors that stimulate these cells to grow and divide. Estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor (HER2) receptors are commonly seen. By identifying these receptors if they are present your physician can prescribe treatments that block them and increase the chance of a cancer cure. 

The “stage” of a cancer is based on its size, if it has spread to the lymph nodes, and if so the amount of spread. The most severe cancers are those that have spread to distant sites such as the brain, bone, and lungs. The lower the stage number the higher chance there is for long-term survival. A low stage cancer may still require aggressive treatment depending on the biopsy results. 

Breast Cancer Treatment and Medication

If you are diagnosed with breast cancer you will always be seen by an oncologist. These doctors are knowledgeable about the many types and locations of breast cancer as well as the surgical and medical options. The exact treatment of breast cancer varies heavily based on its stage, biopsy results, and the location of any masses.

Some cancers that are termed early-stage may be treated with a lumpectomy or a mastectomy which is the removal of just the mass or the entire breast. While this seems extreme research has shown that this leads to the highest rates of survival with certain cancers. With advances in the field of plastic surgery and breast reconstruction, this option is becoming increasingly recommended.

Patients with mid-stage disease with spread to local lymph nodes, or particularly large masses, may require surgery to remove and assess the lymph nodes in the armpit. In these cases, radiation, chemotherapy, and special anti-hormone agents may be recommended. 

The exact chemotherapeutic medications used vary widely and are beyond the scope of any online article. Anti-hormone agents, also known as endocrine therapies, are simpler. If a patient’s cancer shows it is sensitive to a certain hormone, a relevant endocrine therapy will likely be prescribed. 

Endocrine therapy can be an effective systemic treatment in hormone-receptor-positive breast cancer.  Premenopausal women are often treated with ovarian suppression, selective estrogen receptor modulators, and aromatase inhibitors.

• Ovarian suppression may be performed via ablation (e.g., oophorectomy, ovarian irradiation) or with gonadotropin-releasing hormone (GnRH) agonists such as Zoladex(goserelin).
• Selective estrogen receptor modulators commonly include Nolvadex (tamoxifen) and Fareston (toremifene).
• Aromatase inhibitors include Femara (letrozole), Arimidex (anastrozole), and Aromasin (exemestane) – these work by blocking the conversion of androgens to estrogen.

In postmenopausal women who already produce lower levels of hormones, agents such as CDK 4/6 inhibitors plus Femara (letrozole), Faslodex (fulvestrant), or aromatase inhibitors are typically used.  CKD 4/6 inhibitors include Ibrance (palbociclib) or Kisqali (ribociclib).

Patients with HER2+ responsive disease typically receive targeted therapy with ‎Herceptin (trastuzumab). Which specifically targets and deactivates the HER2 receptor. 

References:

1. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002; 347:1233. - https://www.nejm.org/doi/full/10.1056/NEJMoa022152
2. Prum BE Jr, Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002; 347:1227. - https://www.ncbi.nlm.nih.gov/pubmed/12393819