Breast Cancer Notes

Breast Cancer

Overview

• Breast cancer primarily affects women, with about 1% of all cases affecting men.
• It is the second leading cause of death in women, after lung cancer.
• In the US, one in nine women will develop breast cancer in their lifetime, compared to one in twenty in 1960.
• Breast cancer is characterized by abnormal, uncontrolled cell growth arising in the breast tissue.

The Breast

• Breasts are composed of fat, glands, and connective (fibrous) tissue.
• Each breast contains several lobes, which are further divided into lobules ending in milk glands.
• Tiny ducts run from these glands, connect, and terminate in the nipple.
• Infiltrating ductal cancer, occurring in the ducts, accounts for 78% of breast cancers.
• Infiltrating lobular cancer, developing in the lobules, accounts for about 10-15% of breast cancers.
• Inflammatory breast cancer is a rare, serious, and aggressive form that is often misdiagnosed and dangerous.

Inflammatory Breast Cancer

• Rare, serious, aggressive form of breast cancer.
• Looks red (erythema), feels warm.
• Thickening of skin.
• Ridges, welts, and hives may be observed.
• Skin may look wrinkled.
• Sometimes misdiagnosed as infection.

Causes and Risks

• Personal or family history is a significant risk factor.
• Not having children or having the first child after age 30 increases risk.
• Radiation therapy to the chest/upper body is a risk factor.
• Being overweight or obese increases risk.
• Risk increases with age.
• Late menopause increases risk.
• Diets high in saturated fat may increase risk.
• Being female is a primary risk factor.
• Estrogen replacement therapy increases risk.
• The risk of breast cancer increases with age:
  • At age 30, the average woman has a 1 in 280 chance of developing breast cancer in the next 10 years.
  • At age 40, the chance increases to 1 in 70.
  • By age 50, the chance is 1 in 40.
  • A 60-year-old woman has a 1 in 30 chance of developing breast cancer in the next 10 years.
• Factors that lower risk:
  • Being older at first menstruation and having an earlier menopause.
  • Having children before the age of 30 helps.
  • Physically active women may have a lower risk.
  • Preemptive mastectomy.

Symptoms

• Early breast cancer often has little to no symptoms and is not painful.
• Breast discharge, especially if only from one breast or bloody, is a concern.
• Sunken nipple, if a new development, should cause concern.
• Redness, changes in texture, and puckering can be associated with breast cancer.
• Lumps on or around the breast, though most are not cancerous, should be checked.
• Other lumps around the underarm or collarbone that don’t go away should be evaluated.
• Loss of smell?

Metastasis

• The most common sites for breast cancer to metastasize are:
  • Lymph nodes under the arm or above the collarbone on the same side as the cancer.
  • Brain
  • Bones
  • Liver

Epidemiology

• In 2005, an estimated 211,240 new cases of breast cancer were expected in the United States.
• The rate of new cases increased since 1980 but has slowed since the 1990s.
• About 1690 new cases of breast cancer were expected in men in 2005.
• An estimated 40,870 deaths (40,410 women, 460 men) were anticipated from breast cancer in 2005.
• Mortality rates declined 1.4% per year during 1989-1995 and by 3.2% afterward.
• The largest decrease in mortality was in younger women for both Caucasians and African Americans.
• The 5-year survival rate for localized breast cancer has increased from 72% in the 1940s to 97% today.
• Regionally spread cancer drops the rate to 78%.
• Distant metastases drops the survival rate even lower to 23%.

Leading Sites of New Cancer Cases and Deaths 2003 Estimates

• Estimated New Cases
  • Male
    • Prostate: 220,900 (33%)
    • Lung & bronchus: 91,800 (14%)
    • Colon & rectum: 72,800 (11%)
    • Urinary bladder: 42,200 (6%)
    • Melanoma of the skin: 29,900 (4%)
  • Female
    • Breast: 211,300 (32%)
    • Lung & bronchus: 80,100 (12%)
    • Colon & rectum: 74,700 (11%)
    • Uterine corpus: 40,100 (6%)
    • Ovary: 25,400 (4%)
• Estimated Deaths
  • Male
    • Lung & bronchus: 88,400 (31%)
    • Prostate: 28,900 (10%)
    • Colon & rectum: 28,300 (10%)
    • Pancreas: 14,700 (5%)
    • Non-Hodgkin lymphoma: 12,200 (4%)
  • Female
    • Lung & bronchus: 68,800 (25%)
    • Breast: 39,800 (15%)
    • Colon & rectum: 28,800 (11%)
    • Pancreas: 15,300 (6%)
    • Ovary: 14,300 (5%)

Estimated New Cancer Cases and Deaths by Sex, US, 2003

• This section provides a detailed breakdown of estimated new cancer cases and deaths by sex for various cancer sites in the US for 2003.

BRCA1/BRCA2

• BRCA1 was discovered in 1994.
• BRCA2 was discovered in 1995.
• 5-10% of all breast cancer cases are linked to these genes.
• Having a single copy of either mutated gene appears to confer about an 80% chance of developing breast cancer.
• BRCA1 is located on chromosome 17.
• BRCA2 is located on Chromosome 13.
• When found, many researchers thought it would shed light on breast cancer in those patients who did not have the mutated gene.
• Both genes help mediate damage to cell’s DNA, but the exact mechanism is still being studied.
• These genes are tentatively linked to an increased risk for also pancreatic, prostate, and ovarian cancer.
• Research suggests estrogen may play a role. Studies on mice without BRCA but treated with excess estrogen were found to over stimulate genes and proteins in a hormonal activating pathway.
• During embryonic development, one X chromosome is randomly shut down. Cells with mutated BRCA1 have been found to prevent fully shutting down the second X chromosome.
• In men, studies show that BRCA2 mainly causes an increase of risk with a 7% risk of breast cancer by age 80.
• Association between BRCA1 and MBC is less clear.
• Female first-degree relatives of MBC cases are at increased risk of breast cancer.
• Women who have the BRCA1 gene tend to develop breast cancer at an early age.
• Possible BRCA carriers are females whose mother and grandmother have had breast cancer.
• Testing for these genes is expensive and frequently not covered by insurance.
• Women who test positive may have trouble getting or keeping health insurance.

Early Detection

• Early detection is key.
• Methods: Self/doctor examinations, Mammography, Ultrasound, MRI, Biopsy
• Breast self/doctor examination includes visual inspection and careful feeling of the breasts, the armpits, and the areas around the collarbone, looking for lumps or abnormalities around the breast.
• Most lumps are NOT cancerous.
• Best time for examination is immediately after the monthly period.
• Not 100% accurate.
• Mammography is an X-ray picture of the breast taken from several angles by compressing the breast horizontally, diagonally, and sometimes vertically and is not 100% accurate.
• Ultrasound is usually done in addition to the mammogram and shows whether a mass is filled with fluid or solid; cancers are solid and is not 100% accurate.
• MRI (Magnetic resonance imaging) differentiates diseased or dying tissue from normal healthy tissue and is almost 100% accurate.
• Biopsy involves taking a very small piece of tissue from the body for examination and testing by a pathologist and is 100% accurate.
• Self/doctor exams usually only feel lumps after tumor is about 1 inch diameter.
• Mammography & ultrasound detect tumors at about ¼ inch.
• MRI uses cell contrast for excellent detection but costs 8-20 times more then standard mammography.
• 100% assurance on any suspicious lumps can only be obtained by a biopsy.
• The stages 0-IV:
  • Stage 0 is noninvasive breast cancer, that is, carcinoma in situ with no affected lymph nodes or metastasis. This is the most favorable stage to find breast cancer.
  • Stage I is breast cancer that is less than three quarters of an inch in diameter and has not spread from the breast.
  • Stage II is breast cancer that is fairly small in size but has spread to lymph nodes in the armpit OR cancer that is somewhat larger but has not spread to the lymph nodes.
  • Stage III is breast cancer of a larger size (greater than 2 inches in diameter), with greater lymph node involvement, or of the inflammatory type, spreading to other areas around the breast.
  • Stage IV is metastatic breast cancer: a tumor of any size or type that has metastasized to another part of the body (ex. bones, lungs, liver, brain). This is the least favorable stage to find breast cancer.

Treatment

• Radiation
• Chemotherapy
• Vaccines
• Surgery
• Hormonal therapy
  • Tamoxifen (Nolvadex) is the most commonly prescribed hormone treatment.
• Therapeutic Vaccines: Treat existing cancers, are under development, and are aimed at Melanoma, lung, ovarian, prostate tumors.
  • They “Kick-start” immune system, Prevent further growth of existing cancers, Block recurrence of treated cancers, and Kill cancer cells not destroyed by previous treatment.
• HER-2/neu
  • Growth-stimulating protein
  • Normal cells express a small amount on their plasma membranes
  • On surface of breast cancer cells
  • Sends messages from cell to “growth factors” outside cell
  • Overabundant on surface of cancer cells in 30% of women with breast cancer
• HER-2/neu Vaccine:
  • Targets HER-2/neu protein
  • Made from small protein pieces likely to trigger an immune response
  • Contains a drug that helps increase white blood cell counts
  • Monthly shots for six months
  • No serious side effects
• Telomerase Peptide Enzyme
  • Found in over 90% of breast cancer tumors
  • Current vaccine research
  • Study measures tumor cell shrinkage in patients after immune response to an antigen
  • Generate white blood cell attack
• Telomerase Peptide Vaccine
  • Antigen/adjuvant vaccine
  • Uses specific peptide to mobilize the immune system
  • Administered over seven months
  • Produced immune response in breast and prostate cancer patients
  • Temporary tumor regression
  • Little toxicity
• Theratope Vaccine
  • Merck and Biomira
  • Used for metastatic breast cancer
  • Stimulates patient’s immune response to tumor STn marker
  • Cancer associated carbohydrate antigen
  • Vaccine contains synthetic form
  • Phase III tests inconclusive
  • Small subset showed improvement in survival
• Herceptin
  • Type of biologic therapy
  • Breast cancer treatment drug
  • Monoclonal antibody therapy
  • Blocks HER-2/neu
  • Effective in metastatic HER- 2/neu positive breast cancer
  • Little effect with HER-2/neu negative breast cancer
• Surgery:
  • Lumpectomy: removal of the cancerous tissue and a surrounding area of normal tissue
  • Simple mastectomy: removes the entire breast but no other structures
  • Modified radical mastectomy: removes the breast and the underarm lymph nodes
  • Radical mastectomy: removal of the breast and the underlying chest wall muscles, as well as the underarm contents. This surgery is no longer done because current therapies are less disfiguring and have fewer complications.
• BRCA1/BRCA2?
  • No “treatment”
  • Mastectomy cuts risk by 90%
  • Hysterectomy slashes another 50%
  • Tamoxifen:
    • anti-estrogen drug
    • Lowers risk of diagnosis of benign tumors influenced by estrogen
    • Reduces risk about 28%
    • May reduce need for biopsies in high-risk women
    • Intervenes before invasive cancer begins

The Checklist

Age 20-39

• Monthly self breast exam
• Yearly breast exam by doctor
• Mammogram every 2-3 years

Age 40+

• Monthly self breast exam
• Breast exam by doctor every 6 month
• Mammogram once a year
• Skin exam yearly

Conclusion

• The biggest risks for breast cancer are age, sex, and genetics
• Second highest cancer killer in women
• Rates of new cases have slowed
• BRCA1/BRCA2 only effect 5% of cases
• Several early detection techniques and devices
• Vaccines show promise but are not a solution
• Surgery helps prevent reoccurrence.

References

• Listing of references used in the presentation.