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Breast cancer- Basics

Breast cancer -Worldwide most common cancer in women GLOBOCAN reports that female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer with an estimated 2.3 million new cases followed by lung , colorectal , prostate and stomach In UK as rest of the world breast cancer is the most common type of cancer in women Incidence , mortality and survival rates varies significantly among different parts of world but in general developed countries have higher rates of breast cancer than developing countries Less than 10 % of breast cancers can be attributed to an inherited genetic mutations About 1 % of breast cancers happen in males , in the UK about 400 cases are diagnosed / year , this happens more in older male who had hormonal imbalance , exposure to radiation and a family h/o breast cancer -most common risk is a BRCA2 gene mutation Uncommon before age 40 ( < 5 % ) and most frequently diagnosed in women age 55-64. Risk increases with age but the rate at which it increases , decreases after menopause Lifetime risk in UK is 1 in 9 women , in the US this was 12.3 % or about 1. 8 ( US data between 2010-12 )

 

Overall the burden of breast cancer and mortality is growing rapidly worldwide – possibly related to factors which are associated with socioeconomic
 development In UK about 50,000 new cases / year Breast lump is the most common presenting symptom

 

Invasive breast cancer – Most breast cancers are invasive broadly divided histologically into ductal and lobular. Characterized by lack of overall architecture , infiltration of cells haphazardly into a variable amount of stroma , or formation of sheets of continuous and monotonous cells without respect for the form and function of a glandular organ
 Invasive ductal carcinoma ( IDC ) or also known as infiltrating ductal carcinoma is predominant subtype up to 75 % of cases
○ IDC originates from milk ducts and extends to the duct wall , invading the breast fatty tissue and possibly other parts of body Ductal carcinoma of special types -all have underlying IDC-here they are named according to the dominant differentiating feature that they display
○ medullary carcinoma
○ tubular carcinoma
○ mucinous carcinoma
○ Paget’s disease of breast Invasive lobular carcinoma ( ILC ) ranges from 5 % to 17 %
○ about 20 % develop contra-lateral breast cancer
○ can spread to peritoneum , meninges , ovaries and the uterus Mixed ductal and lobular type.

 

Non-invasive breast cancer – Cancer has not extended away from the lobule or ducts where it is situated
 Ductal carcinoma in situ ( DCIS )○ here atypical cells develop within the milk ducts but have not extended to close proximity of tissue or outside
○ limited to breast ducts
○ more morphologically heterogenous in comparison to LCIS
○ 4 types of DCIS are recognised papillary , ciribriform , solid and comedo

 Lobular carcinoma in situ ( LCIS )develops into breast lobules 
○ risk factor for development of BrCan
○ pathologists recognise LCIS by its conformity to the outline of the normal lobule with expanded and filled acini.

 

Molecular subtypes – Molecular analysis of breast cancer subtypes is now quite advanced This is based on gene expression profiling , molecular findings and immunohistochemistry Knowledge of these allow oncologists to offer individualized treatment planning- targeted therapy Different subtypes reflect the biological diversity of breast cancer Estrogen receptor ( ER ) is one of the most important prognostic biomarkers in breast cancer ( up to 80 % of breast cancers are ER +ve and 55 % to 65 % are +ve for PR expression ) The different molecular subtypes are associated with different patterns of local regional recurrence and response to treatment.

 

Risk factors – After gender age is the most imp risk factor -it reaches its peak around menopause and the gradually decreases or remains constant ( very rare below 20 and rare below 30 )

 

Menarche- Historically thought that women with early menarche ( for e.g < 12 compared 
to age 15 ) had increased risk of breast cancer.

A new population based case controlled study where they differentiated reproductive risk factors among different cancer subtypes in women age 20-44 found no statistically significant relation in any of the 3 cancer subtypes.

 

Parity- It is thought historically that early age at first birth and increasing number of full-term births are associated with a long term reduction in risk. Risk may vary between cancer subtypes – may need further study.

 

Pregnancy- Most common cancer in pregnant and post-partum women.

 

Age at 1st birth – Traditionally thought that older age at 1st full time pregnancy is associated with an ↑ ed risk of developing breast cancer.

Some recent studies have failed to show this correlation.

 

Number of live births – Studies have shown that every childbirth reduces the risk of PR+ve and ER+ve cancers by up to 10 %. Parity not found to be associated with hormone receptor negative cancers Another study has shown that increasing number of live births was associated with ↓ BrCan risk in all 3 subtypes but his was only statistically significant in ER+ve BrCan.

 

Abortion- Reported earlier that higher incidence rate of induced abortion was associated with an ↑ed risk of developing BrCan Not proven by prospective quality data.

 

Breast feeding – Considered protective with reduced 
risk.

May not lead to reduced risk in all molecular subtypes.

 

Menopause – Age > 50 was thought to infer increased risk A large collaborative study has shown greater risk of BrCan in premenopausal women than postmenopausal women of same age.

 

Family history- major risk factor in those cases where a hereditary cause is suspected < 30 % of times a causative identifiable gene mutation can be Up to 25 % of hereditary cases are due to a mutation in one of the few but highly penetrant genes ( BRCA1 , BRCA2 , PTEN , TP 53 , CDH1 & STK 11 ) which confers up to an 80 % lifetime risk of BrCan There is an increased lifetime risk of ovarian cancer with about 10-40 % with BRCA1 carriers and 10% to 20 % for BRCA2 carriers.

 

Hormone replacement therapy- Evidence point to an association between HRT use and BrCan This evidence is for combined oestrogen and progesterone formulations in current users which becomes negligible after cessation of treatment Estrogen only HRT -most papers deem this safe as it does not interfere with detection and diagnosis , while others say that the association is not clear It is also reported that duration is important as short term HRT use does not appear to ↑ the risj significantly whereas long term > 5 yrs combined HRT is associated with highest risk.

 

Most asymptomatic in initial stages Generally picked up during routine screening Breast lump is the most common presenting symptom which may be noticed accidentally during combing or showering Breast pain is uncommon but can happen in about 5 % Inflammatory variant may present with swelling / redness and other local signs of inflammation.

 

Consider questioning based on risk factors Ask about
○ when did she notice the lump 1st
○ does she routinely does self examination
○ h/o trauma
○ rapid growth
○ relation to periods
○ previous breast problems
○ nipple changes ( inverted , deviated , discharge )
○ change in appearance of breast / size/redness /pain/ axillary lumps Relation ship to pregnancy / menstrual cycle Skin changes – 
○ carcinoma below the skin can lead to dimpling , puckering , colour changes
○ locally advanced disease may present with peau d’orange ( lymphoedema of the skin ) , frank ulceration Always ask family history including h/o ovarian cancer and breast cancer in 1st degree relatives ( including males ) Systemic symptoms – late presentation but enquire about Medical history H/O thoracic radiation Current medications including OC pill , HRT , steroids , spironolactone.

 

Learn a systematic method of breast examination – respect privacy and chaperone Look for
○ symmetry , deformity , skin changes
○ nipples – retraction , discoloration , inversion , ulceration and eczematous changes Inspect regional L nodes – axillary and supraclavicular If you feel a lump ie a 3 dimensional , distinct from surrounding tissues and asymmetric relative to the other breast- note
◘ size , shape , consistency , texture , tenderness 
◘ fixation to skin or deep tissue
◘ location and relation ship to areola

If doubts remain in pre-menopausal women a repeat examination at a different point in the menstrual cycle could be considered.

 

Triple evaluation is carried using clinical evaluation , imaging and tissue biopsy.

 

Refer 2 weeks USC aged 30 and over with an unexplained breast lump with or without pain OR aged 50 and over with any on one nipple only
○ discharge
○ retraction
○ other changes of concern

 

Consider a USC for 2 weeks appt – kin changes that suggest breast cancer OR aged 30 and over with an unexplained lump in axilla.

 

Consider Non-urgent referral if < 30 and an unexplained breast lump with or without pain.

 

Lump – discreet lump any woman age > 30 that persists after their next period or presents after menopause any age -
○ discrete , hard lump with fixation with or without skin tethering
○ a lump that enlarges
○ persistent focal area of lumpiness or a change in breast texture
○ progressive change in breast size with oedema
○ skin distortion
○ other reasons for concern as family history
○ previous h/o breast cancer who present with a further lump or suspicious symptoms.

 

Nipple symptoms – spontaneous U/L bloody nipple discharge U/L eczematous skin or nipple changes that do not respond to topical treatment nipple retraction or distortion of recent onset B/L nipple discharge -staining clothes blood stained discharge at any age.

 

Males – 50 and over with a U/L firm subareolar mass with or without nipple distortion or associated skin changes.

 

Other symptoms – asymmetrical nodularity that persists at review after menstruation abscess persistently refilling or recurrent cysts intractable pain- not responding to simple measures persistent unexplained axillary swelling

References

  1. Daly C, Puckett Y. Approach New Breast Mass. [Updated 2021 Apr 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560757/
  2. Shiovitz, S, and L A Korde. “Genetics of breast cancer: a topic in evolution.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 26,7 (2015): 1291-9. doi:10.1093/annonc/mdv022
  3. Clinical Guidelines for the Management of Breast Cancer West Midlands Expert Advisory Group for Breast Cancer guidelines-for-the-management-of-breast-cancer-v1.pdf (england.nhs.uk)
  4. Fragomeni, Simona Maria et al. “Molecular Subtypes and Local-Regional Control of Breast Cancer.” Surgical oncology clinics of North America vol. 27,1 (2018): 95-120. doi:10.1016/j.soc.2017.08.005
  5. Tsang, J. Y. & Tse, G. M. (2020). Molecular Classification of Breast Cancer. Advances In Anatomic Pathology, 27(1), 27–35. doi: 10.1097/PAP.0000000000000232.
  6. Alkabban FM, Ferguson T. Breast Cancer. [Updated 2020 Nov 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK482286/
  7. Shah, Rupen et al. “Pathogenesis, prevention, diagnosis and treatment of breast cancer.” World journal of clinical oncology vol. 5,3 (2014): 283-98. doi:10.5306/wjco.v5.i3.283
  8. Sun, Yi-Sheng et al. “Risk Factors and Preventions of Breast Cancer.” International journal of biological sciences vol. 13,11 1387-1397. 1 Nov. 2017, doi:10.7150/ijbs.21635
  9. Momenimovahed, Zohre, and Hamid Salehiniya. “Epidemiological characteristics of and risk factors for breast cancer in the world.” Breast cancer (Dove Medical Press) vol. 11 151-164. 10 Apr. 2019, doi:10.2147/BCTT.S176070
  10. Tao Z, Shi A, Lu C, Song T, Zhang Z, Zhao J. Breast Cancer: Epidemiology and Etiology. Cell Biochem Biophys. 2015 Jun;72(2):333-8. doi: 10.1007/s12013-014-0459-6. PMID: 25543329.
  11. ROJAS, K. & STUCKEY, A. (2016). Breast Cancer Epidemiology and Risk Factors. Clinical Obstetrics and Gynecology, 59(4), 651–672. doi: 10.1097/GRF.0000000000000239
  12. Agarwal, P & Mishra, Anurag. (2016). Approach to A Patient with Breast Lump.

 

 

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