Breast cancer. Etiology 1. Increased exposure to estrogens: A)Estradiol-early menarche ( 55)...

Breast cancer

Etiology1. Increased exposure to estrogens:A)Estradiol-early menarche (<12), late menopause (>55)B)Estrone-overweight womenC)Xeno-estrogens (contraceptives-increase the risk of

breast cancer, cervical cancer and liver cancer, but decrease the risk of endometrial and ovarian cancer)

The three major naturally occurring estrogens in women are estrone (E1)-from fatty tissue, ovaries and adrenalsestradiol (E2)-from the ovaries, adrenals and peripheral conversion of E1estriol (E3)-from placenta and adrenals.

Etiology

2. Lack of breast-feeding 3. Smoking4. Genetic factors:-BRCA1 or BRCA2 mutations*-Lynch syndromes-other yet unidentified genetic risk factors

*The estimated lifetime risk of developing breast cancer for women with BRCA1 or BRCA2 mutations is 40% to 85%.

Etiology

5. Mouse mammary tumor virus

1. Ductal invasive carcinoma 2. Lobular invasive carcinoma

3. Paget’s disease of the nipple

Histological classification of breast cancer-3 main types

Detailed histologic classification of breast cancer-not to memorize

Carcinoma, NOS (not otherwise specified). Ductal.

Intraductal (in situ). Invasive with predominant intraductal component. Invasive, NOS 80% of all breast cancersComedo. Inflammatory. Medullary with lymphocytic infiltrate. Mucinous (colloid). Papillary. Scirrhous. Tubular. Other.

Lobular. In situ. Invasive with predominant in situ component. Invasive.

Nipple. Paget disease, NOS. Paget disease with intraductal carcinoma. Paget disease with invasive ductal carcinoma.

Undifferentiated carcinoma.

Phyllodes tumor. Sarcomas.Primary lymphomas.

Diagnosis of breast cancer-inspection and palpation of the

breasts and axillae• Palpation is best done after the menstrual bleeding,

when the breasts are the softest

Breast inspection and palpation-click on the video

Diagnosis of breast cancer-imaging

• Main breast imaging procedures:1. Mammography2. Ultrasound-for denser breast tissue (younger women,

usually <35 yo)3. MRI- -//-

Diagnosis of breast cancer-biopsy

• Breast tissue sample taking procedures:I. Fine needle aspiration-ABANDONED FOR FINAL

DIAGNOSISII. Core biopsy:1. Palpation guided core needle biopsy 2. Stereotactic core needle biopsy3. Ultrasound guided core needle biopsyIII. Surgical biopsy1. Incisional biospy2. Excisional biopsy

Core biopsy needle or TruCut needle-click on the movie

Biopsy types-click on the video

Diagnosis of breast cancer-additional diagnostic tests

1. Pulmonary radiography (for lung metastases)2. Abdominal ultrasound (for liver metastases)3. Bone scintigraphy (for bone metastases)

Treatment of breast cancer

1. Surgery2. Radiation therapy3. Chemotherapy4. Hormonal treatment5. Treatment with biological agents

Surgery1. Modified radical mastectomy with lymphadenectomy2. Lumpectomy with lymphadenectomy-lumpectomy is appropriate for tumors generally less than

3 cm, except for smaller breasts, when esthetic results cannot be obtained

-not suitable for T4 tumors (fixed to the pectoral fascia, skin or inflammatory breast cancer)

Lymphadenectomy should be performed excising levels 1 and 2 of axillary lymph nodes

Lymphatic drainage of breast cancer

Lymphatic drainage of breast cancer

• Laterally: through the axillary lymph nodes (group 1-2-3 (3=subclavian)) -> supraclavicular lymph nodes

• Medially: through the internal mammary lymph nodes

Sentinel node procedure• Allows identification of the first draining

lymph node1.Lymphoscintigraphy (Filtered Sulfur Colloid

tagged with the radionuclide Technetium-99m)

2.Methylene blue dye

Radiotherapy

• Adjuvant after lumpectomy for the remaining breast

• Adjuvant for the axilla and supraclavicular lymph nodes, if certain risk factors are present

Chemotherapy

• For almost all breast tumors larger than 2 cm• Increases cure rates• Given neoadjuvantly for large tumors

frequently allows for ulterior lumpectomy

Hormonal treatment

• Given for patients with tumors with positive hormone receptors (estrogen and/or progesterone)

• It needs to be given for more than 5 years• 3 main types of hormonal treatments:1.LHRH receptor agonists2.Aromatase inhibitors3.Tamoxifen

1. LHRH (LH releasing hormone) receptor agonists

• act in the pituitary gland

• act first as agonists and create an LH surge, but block the LHRH receptors and thus decrease LH secretion and thus ovarian estradiol

2. Aromatase inhibitors

• Inhibit the formation of estradiol in the ovaries

AROMATASEINHIBITORS

3. Tamoxifen

• Partial antagonist and agonist • Antagonist on estrogen receptors from breast

tissue

• Agonist on estrogen receptors from bone=> no osteoporosis is produced as with the first 2 treatments

Biologic treatments

• Herceptin=monoclonal antibody that blocks the HER2/neu growth factor receptor

• It is over-expressed in aprox. 30% of early breast cancers

Reconstructive surgery

I. Immediate (at the time of the mastectomy)-musculo-adipose flapsII. Delayed-musculo-adipose flaps-submuscular silicone gel-/saline-filled implants

after stretching the overlying tissue with a tissue-expander over a period of weeks/months

Follow-up• Evidence from randomized trials indicates that periodic

follow-up with bone scans, liver sonography, chest x-rays, and blood tests of liver function does not improve survival or quality of life when compared to routine physical examinations.

• Based on these data, some investigators recommend that acceptable follow-up be limited to physical examination and annual mammography for asymptomatic patients who complete treatment for stage I to stage III breast cancer.

The risk of a primary breast cancer in the contralateral breast is approximately 1% per year.

Screening of breast cancerScreening of breast cancer with mammography

decreases breast cancer mortality*• For medium risk women:- Mammography from age 40, indefinitely,

annually [American Cancer Society American College of Radiology (ACR), Society of Breast Imaging (SBI)]

- OR: Mammography age 50->74, biannually [US Preventive Services Task Force (USPSTF) ]

• For high risk women (BRCA1 or BRCA2 mutation carriers or untested first-degree relatives of a BRCA mutation carrier) :

- Mammography from age 30

* 2009 Cochrane review estimated that mammography resulted in a relative risk reduction of death from breast cancer of 15% or an absolute risk reduction of 0.05%

Questions

1. Which are the etiologic factors (risk factors) of breast cancer?

2. Which are the steps of diagnosis of breast cancer?3. What are the main types of treatment of breast cancer?4. What is the screening procedure for breast cancer and

when should it be started?