Breast Cancer - Risk Factors and Treatment

Pearls: 

1. Most women (75%) with breast cancer do not have identifiable risk factors    
2. Early findings: single, nontender, firm to hard mass with ill-defined margins; mammographic abnormalities and no palpable mass
3. Late findings: skin or nipple retraction; axillary LAN; breast enlargement, erythema, edema, pain; fixation of mass to skin or chest wall.
4. Do not ignore breast skin changes or changes to the nipple.
5. Remember how common breast cancer is – the lifetime risk of a woman developing breast cancer is about one in six, making it the most common female cancer in the US and second most common cause of cancer death.

 

 

Risk Factors (this is not an exhaustive list):
1.  Gender – 100 times more common in women than in men
2.  Race – highest incidence in Caucasians, but blacks have higher mortality
3.  Personal history of breast cancer – drastically increases risk of contralateral breast cancer
4.  Lifestyle – alcohol, possibly increased fat intake lead to increased risk, smoking
5.  Hormones – Basically longer lifetime exposure to estrogen leads to increased risk,
a.  Early age of menarche (under 12)
b. Late age of menopause (after 50)
c.  Nulliparity
6.  Family history – but only ~15-20% of patients with breast cancer have a positive family history.
** Only ~5% of cases are attributable to specific mutations (i.e. BRCA 1 and 2, P53, etc) **
7.  Radiation exposure – i.e. as treatment for Hodgkin’s lymphoma earlier in life.

 

 

Important Factors in Determining Treatment and Prognosis:
1) Lymph Node involvement – basically, if any lymph node is positive, this means the patient needs adjuvant systemic chemotherapy of some sort.
2) Stage – obviously this plays into treatment and prognosis, and lymph nodes are part of the staging as is tumor size and extension into chest wall or skin, and presence of metastases.
3) Hormone Receptor Status (ER/PR positive vs negative) – generally, presence of ER/PR implies a better prognosis than ER/PR negative cancer, mainly due to the ability to treat with endocrine therapy (tamoxifen, aromatase inhibitors).  Also, emerging data that ER/PR positivity also correlates with improved responses to chemotherapy. 
4) HER2 status - ~20% of cancers have overexpression of HER2.  Traditionally thought to represent a poorer prognosis but much of that data was before the emergence of Trastuzumab (Herceptin) which is a monoclonal Ab vs HER2. 

 

Endocrine Therapy for ER/PR + breast cancers:

• Historically related to evidence of regression of breast cancer after oopherectomy; initial therapies were surgical (resection of adrenal gland, pituitary gland or ovaries).  This was followed by high-dose estrogen suppression (ie. DES).
• Better side effect profile than systemic chemotherapy, so it is chosen as first line tx with slowly progressive disease, non-life-threatening visceral involvement, and minimal symptoms, even if the breast cancer has low ER expression
• Tamoxifen
• Selective estrogen receptor modulator
• Tissue-selective estrogen agonist or antagonist
• Beneficial effects of estrogen includes decreased bone demineralization, but also associated with increased risk of VTE, endometrial ca
• Has a more favorable side effect profile than high dose estrogen
• initially used for tx of pre and postmenopausal women with hormone responsive breast cancer
• administration is oral, daily
• first-line agent for adjuvant endocrine tx in premenopausal women
• appropriate for postmenopausal women who have a disease relapse within 12 months of receiving adjuvant therapy with an AI
• Fulvestrant (faslodex)
• Selective estrogen receptor downregulator or "pure" anti-estrogen
• Competes with estrogen at the ER
• Administration is monthly IM injections
• Clinical trials have shown fulvestrant to be as effective as an AI in post-menopausal women with tamoxifen-resistant breast ca
• Limited to postmenopausal women
• Aromatase Inhibitors (AIs)
• anastrazole, letrozole and exemestane
• estrogen depletion therapy
• after menopause, relative secretion of estrogen at extragonadal sites is increased (non-ovarian estrogens predominate)
• aromatase is an enzyme involved in steroidogenesis, which converts adrenal androgenic precursors to estrogen in peripheral tissues (adipose tissue, liver, brain etc.)
• AIs work by decreasing circulating estrogen in postmenopausal women and may also have a direct inhibitory effect on breast cancer cells
• more effective as first line tx (c/w tamoxifen) in postmenopausal women
• can be used in premenopausal women, in combination with ovarian suppression via oophorectomy or GnRH
• Estrogen deprivation therapy in premenopausal women
• Alternative to tamoxifen as first line tx
• Standard of care when relapse on tamoxifen in <1 yr
• Can be accomplished by ovarian ablation (radiation), oopherectomy
• or temporarily by GnRH agonists (goserelin, leuprolide), which are analogs of LHRH, which act on the pituitary to stimulate FSH and LH secretion and profoundly suppress the pituitary-ovarian axis, resulting in a fall in estrogen levels to postmenopausal levels
• often used with tamoxifen, although no clear survival advantage

2) Systemic Chemotherapy – used for ER/PR negative cancers, more controversial for ER (+) cancer, especially if nodes are negative.  Most regimens are anthracycline-based.

3) Trastuzumab (Herceptin) – anti-HER2 monoclonal Ab that also carries a risk of cardiotoxicity, which can be problematic when combined with anthracyclines. 

 

 

Infiltrating lobular breast cancer:

• Second most common type of invasive breast cancer, but only accounts for 5-10% of all breast cancer (after ductal, which accounts for 70-80% of all breast cancer)
• Most lobular cancers are difficult to detect both clinically and radiographically, as they do not have a discrete “edge” or border; unlike ductal carcinoma, there is no associated necrosis or fibrotic response, so there is often not a palpable mass
• cancer can spread insidiously throughout the breast, along the lobules and adipose tissue; on mammography, appearance is more subtle, as it is mostly causes microcalficications (rather than a spiculated mass)
• more often occusr in older women; can present bilaterally
• almost always ER-positive
• most often metastasizes to serosal surfaces (ie. pleural, pericardium), bone and GI tract (less commonly to solid organs)
• treatment for metastatic disease is often with hormonal therapy alone, which is better tolerated than chemotherapy and slows disease progression.  Early aggressive therapy is usually not necessary as major organs are often spared from metastases

 

 

(Katharine Cheung MD, 8/2/10)

(Victoria Kelly MD, 10/5/10)

(Chanu Rhee MD, 1/14/11)