BREAST CANCER
· Breast cancer is the most commonly diagnosed cancer among women in the United States and worldwide (excluding skin cancer).
· a woman in the United States has a 1 in 8 chance of developing invasive breast cancer during her lifetime. This risk was about 1 in 11 in 1975
· Breast cancer is the second leading cause of cancer death for women in the U.S (after lung cancer);
· 12% of women diagnosed with invasive breast cancer die from the disease within five years; at ten years, 20% will have died
· Between 1990 and 2002, the mortality rate for women of all races combined declined by 2.3% annually.
Risk factors
HIGH RISK - relative risk greater than 4
1. Advanced age - more than 70 per cent of cases occur in women over 50 years of age.
2. BRCA gene positive
3. High premenopausal blood insulinlike growth factor (IGF)–1 level
4. High postmenopausal blood estrogen level
5. History of mother and a sister with breast cancer
6. Syndromes
o Li Fraumeni – characterized by a mutation of TP53, is associated with multiple cancers, including the SBLLA syndrome (sarcoma, breast and brain tumors, leukemia, laryngeal and lung cancer)
o Muir Torre syndrome – characterized by a mutation of MSH2 gene, sebaceous carcinoma with visceral carcinoma (colon, genitourinary, breast, lymphoma)
o Cowden disease - papillomatosis of the lips and oral mucosa, multiple facial trichilemmomas, and acral keratosis. The prevalence rate of breast cancer in women with this disease is 29%
MODERATE RISK - relative risk of 2-4
1. High socioeconomic status
2. Age at first full-term pregnancy older than 30 years
3. History of cancer in one breast
4. Any first-degree relative with a history of breast cancer
5. Hormone replacement therapy - long-term use of HRT after menopause, particularly estrogens and progesterone combined increases risk of development and likelihood that the cancer would be found at a more advanced stage
6. History of a benign proliferative lesion, dysplastic mammographic changes, and a high dose of ionizing radiation to the chest
POPULATION RISK - relative risk of 1.1-1.9
1. Nulliparity
2. Early menarche (age <11 y)
3. Late menopause (age >55 y)
4. Postmenopausal obesity
5. High-fat diet/saturated fat–rich diet
6. White race - Older than 45 years
7. Black race - Younger than 45 years
8. History of endometrial or ovarian cancer
9. OCP use
10. Alcohol intake
Identified factors with a protective role against breast cancer
1. Age at first period older than 15 years
2. Breastfeeding for longer than 1 year
3. Monounsaturated fat–rich diet
4. Physical activity
5. Premenopausal obesity
· A previous cancer in one breast doubles the risk of developing a cancer in the other breast.
· Estrogens, by their proliferation-promoting effect on the breast epithelium later, increase the chance of DNA replication errors leading to carcinogenic mutations.
· Early menarche, regular ovulation, and late menopause increase lifetime exposure to estrogens in premenopausal women, while obesity and hormone replacement therapy increase estrogen levels in postmenopausal women. Conversely, late menarche, anovulation, and early menopause (spontaneous or induced) are protective, owing to their effect on lowering the level or shortening the duration of estrogenic exposure.
· Lactation and premenopausal obesity are associated with lower estrogen levels as a result of anovulation.
· in younger women, tumours are likely to be larger and more aggressive and overall survival is lower than for older women with the disease.
· Other pathologic indicators of increased risk of breast cancer are:
1. Multifocal tumours
2. Lobular carcinoma in-situ (LCIS)
3. Multiple areas of in-situ intra-ductal carcinoma, (DCIS)
4. Changes of epithelial hyperplasia and atypias
Genetic Factors
· Breast cancer has a definite inheritance pattern:
Relation / Relative Risk /Affected first degree relative (mother or sister) / 2.3
Affected mother and sister / 14
Affected second degree relative (aunt / grandmother) / 1.5
· Hereditary breast cancers represents 5-26% of all breast cancers.
· The mutated genes BRCA1 and BRCA2 are responsible for approximately 30-40% of inherited breast cancers.
· 50-87% of women carrying a mutated BRCA1 gene develop breast cancer during their lifetime.
· BRCA2 mutations are associated with other types of cancers, such as ovary, pancreatic, fallopian tube, bladder, non-Hodgkin lymphoma, and basal cell carcinoma.
· In males, BRCA2 is associated with male breast cancer and prostatic cancer
SCREENING
· Benefits of early detection include increased survival, increased treatment options and improved quality of life.
· Components
1. breast awareness/ Breast self-examination (BSE)
o awareness by a woman of the normal look and feel of her breasts
o Simple, non-invasive and cheap., Most breast cancers are initially detected by the patient.
o Patients who do BSE are more likely to present with a smaller stage I tumour, LN involvement is less frequent, and survival rates are longer than those who don’t.
2. clinical breast examination
o there is no evidence of any additional benefit of clinical breast examination for women who are already attending for regular screening mammography.
3. Mammography
o Population-based screening using mammography is the best early detection method available for reducing deaths from breast cancer
o Evidence of the benefit is strongest for women aged 50–69 years. No evidence that population-based screening mammography is beneficial for women younger than 40 years
o In Australia, even with a fully implemented mammographic screening program, more than half of breast cancers are diagnosed after investigation of a breast change found by the woman or by her doctor.
Recommendations of the National Breast Cancer Center (www.nbcc.org.au)
Breast Awareness
· recommended that women of all ages, and regardless of whether they attend for mammographic screening, are aware of how their breasts normally look and feel and report any new or unusual changes promptly to their general practitioner.
Clinical breast examination
· Women who are eligible and are attending for regular mammographic screening should be aware that there is no evidence that clinical breast examination will provide additional benefit.
Mammographic study
Women younger than 40 years
· Mammographic screening is not recommended for women younger than 40 years of age.
Women aged 40–49 years
· Women aged 40–49 years are eligible for free two-yearly screening mammograms through the BreastScreen Australia Program (although they are not targeted by the Program).
· In deciding whether to attend for screening mammography, women in this age group should balance the potential benefits and downsides for them, considering the evidence that screening mammography is less effective for women in this age group than for older women.
Women aged 50–69 years
· It is recommended that women aged 50–69 years attend the BreastScreen Australia Program for free two-yearly screening mammograms.
Women aged 70 years and older
· Women aged 70 years and older are eligible for free two-yearly screening mammograms through the BreastScreen Australia Program (although they are not targeted by the Program).
Management of women at high risk (>4x)
· BRCA gene positive. Options:
1. Increased surveillance
o Annual mammography >35yo
o Annual ultrasound
o Consider MRI - most sensitive investigation (97%)
o Yearly clinical examination
2. Chemical prophylaxis
o Tamoxifen - studies suggest that the drug tamoxifen reduces the five-year risk of breast cancer in high-risk women. However, it is still unknown whether tamoxifen can reduce breast cancer risk specifically in women who carry a BRCA1 or BRCA2 mutation.
3. Surgery
o Oophorectomy – reduce risk by 50%
o Bilateral prophylactic mastectomy
§ reduce risk by >95% if nipple preserved
§ >99% if nipple not preserved
CLINICAL
· Many cases are now detected earlier because of routine screening, including mammography
· The commonest presentation is as a painless mass:
· Usually upper outer quadrant (most breast tissue)
o Upper outer > central > upper inner > lower outer > lower inner
· Regional LN mets may indicate biological aggressiveness, high likelihood of recurrence or regional mets.
· Mets: bone, lung, liver, brain and spinal cord, adrenal
· Nipple discharge: bloody, serous, milky or mixed. Spontaneous more significant than expressed.
DIAGNOSIS
Standard battery of tests is known as the Triple Test
1. Physical examination
2. Mammogram and/or US - Alternative to mammogram in young women. Useful for cysts.
3. FNAB - The most valuable way of assessing breast thickening and masses.
Probability of cancer is low if all three tests are negative and risk factors are low.
Other diagnostic tests:
1. Core needle biopsy- Allows better histological assessment than FNAB.Used when FNAB results unclear
2. Breast biopsy uncer stereotactic(hook wire biopsy) or US guidance
3. Excision biopsy (+ frozen section)
o Plan incision for future excision with skin sparing mastectomy
· Findings of atypical ductal or atypical lobular hyperplasia in an otherwise benign needle core biopsy mandate that additional tissue be obtained. A significant proportion will have carcinoma in adjacent tissues
· Test for metastasis – not routine but directed by patient’s symptoms
Cellular Classification
1. Ductal (70-80%)
2. Lobular
3. Nipple – Paget’s disease
a. Histologically, the disease is localized to the epithelium of the nipple-areola complex and the characteristic cells, or Paget cells, are contained within the basement membrane
Other tumor subtypes that occur in the breast but are not considered to be typical breast cancers:
1. Cystosarcoma phyllodes.
2. Angiosarcoma.
3. Primary lymphoma.
STAGING
AJCC 2002 staging – complex
Refer to link
Prognostic factors
1. Lymph node involvement - The number of positive nodes is the best single prognostic factor.
2. size of tumor (>2cm)
3. age of patient (younger age worse)
4. histologic grade - based on the degree of tubule formation, number of mitoses, and nuclear pleomorphism (combined into the Bloom-Richardson (B-R) grade)
5. ER status
Pregnancy
· Studies indicate that women who have TRAM flap reconstructions may successfully undertake pregnancy with little risk to the baby.
· However there may be reasons to do with management of breast cancer that limit this option and this should discuss this with an Oncologist.
· It is also not advisable to fall pregnant for about one year at least after TRAM flap reconstruction to reduce the risk of hernia formation, which is greater if pregnancy occurs, even years after the reconstruction.
Prophylactic Mastectomy
· Indicated for very high risk group – ie hereditary breast cancer (BRCA1/2)
· Younger women tend to choose this operation
· 1% risk of breast cancer after bilateral prophylatic mastectomy (Mayo clinic 636 women)
· estimated risk reduction from these studies is 80 percent to 95 percent.
· life expectancy is believed to be increased from 2.9 to 5.3 years.
· 70% women satisfied
· 74% reported a diminished level of emotional concern about developing breast cancer.
· in women with very large (D cup or greater) and ptotic breasts, there is a significant surgical and cosmetic liability to performing a subcutaneous mastectomy. In these women, a simple mastectomy often with further reduction of the breast skin envelope is recommended
TREATMENT
DCIS
· noninvasive, precancerous condition. DCIS can progress to become invasive cancer, but estimates of the likelihood of this vary widely.
· Due to 30% incidence of multicentric disease, lumpectomy alone is associated with local recurrence (25-50%)
Treatment options for patients with DCIS
1. Breast-conserving surgery and radiation therapy, with or without tamoxifen.
§ cumulative incidence of recurrent ipsilateral breast cancer was reduced from 26% to 12% by the addition of radiation to surgery.
§ With tamoxifen, ipsilateral invasive breast cancer decreased from 4.2% to 2.1% at 5 years. Tamoxifen also decreased the incidence of contralateral breast neoplasms (invasive and noninvasive) from 0.8% per year to 0.4% per year). The benefit of tamoxifen extended to those patients with positive or uncertain margins
2. Total mastectomy with or without tamoxifen.
3. Breast-conserving surgery without radiation therapy. A large national clinical trial comparing breast-conserving surgery and tamoxifen with or without radiation therapy is currently under way.
LCIS
· LCIS is not known to be a premalignant lesion, but rather a marker that identifies women at an increased risk for subsequent development of invasive breast cancer. This risk remains elevated even beyond 2 decades, and most of the subsequent cancers are ductal rather than lobular.
· Most women with LCIS can be managed without additional local therapy after biopsy. No evidence is available that re-excision to obtain clear margins is required.
· Tamoxifen has decreased the risk of developing breast cancer in women with LCIS and should be considered in the routine management of these women
Treatment options for patients with LCIS
1. Observation after diagnostic biopsy.
2. Tamoxifen to decrease the incidence of subsequent breast cancers
3. Ongoing breast cancer prevention trials.
4. Bilateral prophylactic total mastectomy, without axillary node dissection.
Paget disease
· mastectomy should be performed in patients with a tumor located beyond the central portion of the breast,
· Breast conservation may be considered in patients with disease limited to the retroareolar area, with excision of the nipple-areolar complex and complete excision of the mammographic abnormalities with a 2-cm cone of the retroareolar tissue.
· If surgical margins are negative, radiotherapy should complete the treatment; otherwise, mastectomy is the treatment of choice.
Stage I, II, IIIA, and Operable IIIC Breast Cancer
Surgical options
1. Breast-conserving therapy (lumpectomy, breast irradiation, and surgical staging of the axilla).
2. Modified radical mastectomy (removal of the entire breast with level I-II axillary dissection) with or without breast reconstruction.
a. skin sparing (for T1 or T2 tumors only)
b. skin and nipple sparing (for T1 or T2 tumors only)
· Axillary staging for (level II)
1. any invasive disease
2. widespread DCIS
· SLNB
1. done within trial setting
2. for invasive tumors <2cm or extensive DCIS
3. studies demonstrate a 97.5% to 100% concordance between SLN biopsy and complete axillary lymph node dissection.