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Breast Cancer (BCa)

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Introduction:

  • Most common cancer among females worldwide.

  • Leading cause of cancer death in Saudi Arabia and the 2nd in many western countries (including US, UK, and Canada). Decreased incidence and mortality in the US and Western Europe lately due to: less HRT use, early detection through mammography screening, & appropriate use of systemic adjuvant therapy.

  • Majority of breast cancers arise from: epithelial cells of the milk ducts (Ductal carcinomas).

  • Most common site for breast cancer is the upper outer quadrant, including the axillary tail.

 

Risk Factors:

  • Gender:

    • Being a female is the single most significant risk factor for breast cancer in general.

  • Age:

    • E.g.: a newly developed mass in a 75 years old female has high risk of malignancy; however, the same mass in a 32 years old is not highly concerning.

  • Family history:

    • Especially in first-degree relatives.

    • Onset of breast cancer in the family in premenopausal period.

  • Genetic:

    • BRCA1

    • BRCA1

    • P53 germ line mutation

    • PTEN

    • CHEK2

  • History of previous benign breast pathology:

    • Especially proliferative benign lesions.

  • Total duration of estrogen exposure:

    • Parity after the age of 20.

    • Early menarche (regular cycles) before the age of 13 Y/O.

    • Late menopause after the age of 55 Y/O.

    • Exogenous use of estrogen (OCPs and HRT).

  • Others:

    • Previous radiation therapy to the chest area.

    • Alcohol consumption.

Pathophysiology:

  • More than 80% of all breast cancer cases are sporadic.

  • Familial (hereditary) breast cancer cases, in which 80% of those are caused by BRCA1 & BRCA2.

  • Hereditary Breast Cancer (all are autosomal dominant):

Protective factors: Breast feeding, active lifestyle, soy, early menopause, and early childbirth.

Study guide:

Table 1: Adopted from Cecil Medicine, edited by LtMed.

  • Molecular Mechanism of Carcinogenesis:

    • Hormone receptors have high predictive for treatment response:

      • Estrogen receptor positive (ER+): common in postmenopausal (2/3) cancer patients.

      • Progesterone receptor positive (PR+).

      • Human epidermal growth factor receptor 2 positive (HER2+, or HER2/neu+).

Types of Breast Cancer (Histology)

Pre-invasive

Ductal carcinoma in situ

Ductal carcinoma in situ

Invasive ductal carcinoma "most common type 80%"

Invasive lobular carcinoma 

Mucinous (Colloid)

pH low

Tubular

Papillary

Medullary

Cribriform

Pre-invasive

Invasive

Paget disease of the nipple

Tubular

Inflammatory carcinoma 

Intrensic subtypes (TCGA)

Luminal A: ER+

Better prognosis

Luminal B:

ER+, HER2/neu

overexpression

Basal-like:

ER & HER2/NEU

negative

HER2+

overexpression:

ER negative

Common with BRCA1

Worst prognosis

Types of breast cancer according to histology:

Types of

​

​

​

Breast Cancer

 

 

 

 

(Histology)

Pre-invasive

Invasive

Ductal Carcinoma

in situ

Lobular Carcinoma

in situ

Paget disease of the

nipple

Invasive Lobular

Carcinoma

Tubular

Inflammatory

Carcinoma

Invasive Ductal

Carcinoma

(Most common type 80%)

Mucinous (colloid)

Papillary

Medullary

Cribriform

Osmotic Gap 50-100 mosm \ Kg

> 100 Osmotic Diarrhea 

normal pH: 7-7.5

pH high

pH low

Ions

Sugar

<50 

Secretory Diarrhea

Table 2: Adopted from USMLE step 2 CK, and Organ System. Edited by LtMed.

Clinical Presentation:

  • >80% of all breast masses are benign.

  • Malignancy is highly suspect if any of the following is present:

    •  Lump: solitary, hard, painless, irregular & fixed to the skin or chest wall.

    •  Skin dimpling or skin changes (redness, swelling, dimpling etc.).

    •  Recent nipple retraction, inversion, or ulceration.

    •  Nipple discharge: especially bloody discharge!

  • Signs & symptoms of metastasis:

    • Bone (bone pain) most common site of metastasis.

    • Lungs (pleural effusion).

    • Liver (abdominal pain).

    • Brain (headache & visual disturbance).

Figure 1:

Signs & Symptoms

of Breast Cancer

Diagnosis:

  • The “Triple Assessment” Method:

  1. Clinical breast examination.

  2. Radiology assessment (any of the following, described with BIRADS classification):

    1. Ultrasound if <35 years old (cystic vs. solid mass)

    2. Mammography if > 35 years old. (**Majority of screening mammograms falls into BIRADS I, or II.)

    3. Magnetic Resonance Imaging

  3. Biopsy:

    1. ​Core/ true cut biopsy:

      1. The best modality of biopsy to confirm the diagnosis and type of breast cancer (invasive vs. in situ).

      2. Determines the predictive factors e.g.: ER/PR, HER-2 etc.

    2. Fine needle aspiration (FNA):

      1. Not usually used except if high suspicion of benign mass.

  • Other workup:

    • Pan-CT to check for metastasis.

    • Bone scan: reserved for patients with bone pain.

    • Glactogram for nipple discharge.

  • Blood tests:

    • Tumor marker CA 15-3: to assess the progression and response to treatment.

    • BRCA mutation testing:

      • For women < 50 Y/O, or high risk family history, and men with breast cancer.

Table 3: BIRADS Classification for Breast Imaging Report.

Figure 2: BIRADS V.

Screening:

  • Mammography:

    • The modality of choice for screening patients > 40 Y/O.

    • Age of maximum benefit to start mammogram screening is 50 Y/O.

    • Repeated every 2 years and stopped at age of 75 Y/O if no abnormalities detected.

    • Mammogram is the only screening modality that lowers mortality in breast cancer.

  • Ultrasound is used for screening patients < 35 Y/O.

  • Management:

  • Surgery:

    • Breast conserving surgeries (BCS):

      • Lumpectomy, or partial mastectomy.

    • Mastectomy:

      • Total mastectomy.

      • Radical mastectomy.

      • Modified radical mastectomy (MRM).

  • Radiation therapy:

    • Especially after surgery (reduces risk of recurrence by 70%).

  • Chemotherapy:

    • Neoadjuvant or adjuvant.

  • Hormone receptor blockers (used in cases of ER+, or PR+):

  • Tamoxifen:

    • Selective estrogen receptor modulator.

    • Best used for premenopausal women.

    • S/E:

      • Increases risk of DVT, and PE.

      • Increases risk of endometrial cancer.

  • Aromatase inhibitors (Anastrozole and Exemestane):

    •  Inhibiting aromatase enzyme thus preventing the conversion of substrates to estrogen.

    •  Best used for postmenopausal women.

    •  S/E:

      • Increase risk of osteoporosis.

  • Monocolonal antibodies/target therapy (Trastuzumab):

    • Used in advanced metastatic disease.

  • Management of complications:

    • Bisphosphonate:

      • For prevention and treatment of bone pain.

      • For treatment of bone metastasis hypercalcemia.

    • Low-molecular weight heparin:

      • To prevent DVT/PE with the treatment of Tamoxifen.

Treatment of Breast Cancer According to the Staging:

Prognosis:

  • Axillary lymph node involvement is the most useful factor for prognosis.

  • Poor prognostic factor in breast cancer:

    • Young age

    • Premenopausal

    • Large tumor size

    • High tumor grade

    • ER, PR, HER2 receptor positive Positive lymph nodes

References:

  1. Goldman L, Schafer A. Cecil Medicine. London: Elsevier Health Sciences; 2011.

  2. Walker B, Colledge N, Ralston S, Penman I. Davidson's principles and practice of medicine.

  3. Kumar P, Clark M. Kumar & Clark's clinical medicine.

  4. Le T, Bhushan V, Singh Bagga H. First aid for the USMLE step 2 CK. New York: McGraw-Hill Medical; 2010.

  5. Le T, Krause K. First aid for the basic sciences. New York: McGraw-Hill Medical; 2012.

  6. Perez M, Botsford L, Liaw W. Déjà review. New York: McGraw-Hill Medical; 2011.

  7. Reid M, Stehr W. The Mont Reid surgical handbook.

  8. Fischer C. Master the boards.

  9. Understanding Breast Cancer About Causes, Symptoms and Signs, Diagnosis, And Treatment [Internet].

    gadogadohealth.com. 2016 [cited 28 March 2016]. Available from: http://gadogadohealth.com/understanding-

    breast-cancer-about-causes-symptoms-and-signs-diagnosis-and-treatment/ (Figure 1).

  10. Weerakkody Y. Breast imaging-reporting and data system (BIRADS) | Radiology Reference Article |

    Radiopaedia.org [Internet]. Radiopaedia.org. 2016 [cited 28 March 2016]. Available from: http://radiopaedia.org/articles/breast-imaging-reporting-and-data-system-birads (Figure 2).

Written by: Lama Al Luhidan

Reviewed by: Haifa Al Issa and Roaa Amer

Format editor: Roaa Amer

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