Presentation

• An erythematous ‘eczema-like’ rash, usually unilateral.
• Itchy, inflamed nipple
• Burning sensation
• Discharge from the affect area
  • May also be discharge from the nipple related to the underlying cancer
• Inverted nipple

Pathology

Investigations and treatment

• In the penis it is extremely rare
• Primary cases do exist – and are treated with local excision

• Paget’s typically starts at the nipple and works outwards
• Eczema starts at the periphery of the areolar and works inwards

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

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• Hyperandrogenism
  • Hirsutism – male pattern hair growth / excessive female hair growth, acne, deep voice, oily skin
• Polycystic ovaries
• Oligo-ovulation
• Insulin resistance – weight gain
• Can also be caused by Cushings, and adrenal hyperplasia

Epidemiology

• Polycystic ovaries are a common finding on USS – affecting up to 1/3 of women of reproductive age. However, most women with polycystic ovaries do not exhibit the other systemic features required for a diagnosis of PCOS
• True PCOS effects 5-15% of women aged 18-45
• It is the most common endocrine disorder in reproductive age women

Aetiology

• Essentially unknown – probably multifactorial
• Seems to have a familial link – the exact cause of which is yet unknown
• SMOKING
• Possibly insulin resistance
  • There is certainly a relationship between the two – hard to determine cause and effect
  • Insulin resistance is also associated with obesity – and excess adipose tissue will result in the creation of excess oestrogen – a vicious cycle

Pathophysiology

• Excess androgen production by the ovaries
  • Produced by theca cells in the ovaries
  • Thought to be a result of increased LH levels and / or hyperinsulinaemia
• Insulin resistance
  • Resulting in hyperinsulinaemia
  • Hyperinsulinaemia in turn causes increased androgen production
    • In many women total testosterone levels are not raised, but free testosterone levels may be raised, due to a decrease in production of sex hormone binding globulin by the liver (SHBG)
• Weight further increases insulin resistance
• Raised LH production in the anterior pituitary gland
• PCOS can exist without cysts in the ovaries – when the underlying metabolic disturbances are present alone
  • The cysts seen on USS are actually immature follicles and not true cysts
  • Cysts are about 2-6mm in size
• PCOS can exist without raised androgen levels

Presentation

Typically presents between mid teens and mid 20s. Symptoms may include:

• Amenorrhoea
• Oligomenorrhoea
  • Defined as <9 periods per year
  • Due to anovulation (irregular / absent ovulation)
  • The anovulation can also result in reduced fertility
• Acne
• Weight gain / insulin resistance
  • There may be associated sleep apnoea
• Psychological symptoms
  • Mood swings
  • Depression
  • Anxiety
  • Low self-esteem
• Acanthosis nigricans –  dark patches of skin, particularly on the neck and in skin folds – secondary to insulin resistance
• Masculinisation – due to excessive testosterone production
  • E.g. Hirsutism – male pattern hair growth on females. Common during puberty as the hormonal axis matures, and usually transient. If persistent, or presents later in life, suspect another cause (e.g. testosterone producing tumour)
  • Male pattern balding
  • Acne
• Infertility and sub-fertility may occur – although it is often treatable. Reassure patients at the time of diagnosis that many women conceive naturally (even those who do to have regular periods) and many more can conceive with medical assistance to achieve ovulation
  • Concerns about fertility are often the most important concern for newly diagnoses patients

Symptoms usually begin around the time of puberty, and worsen at the patient gets older.

• PCOS is unlikely if regular periods have been established before amenorrhoea.

Diagnostic Criteria

According to the Rotterdam criteria at least TWO of the following is diagnostic:

• Polycystic ovaries
  • 12 or more peripheral follicles, OR
  • Ovarian volume >10 cm³
• Clinical or biochemical signs of hyperandrogenism
• Oligo-ovulation (<9 periods per year) or anovulation

Note that these criteria do not necessarily require any formal investigations.

However – be wary of diagnosing teenage girls with PCOS based purely on the above criteria. Symptoms of puberty (such as acne, and irregular periods) can mimic those of PCOS. Also, in women with <8 years of ovulation, the ovaries may appear to have multiple follicles on USS. As such, a 2017 international consortium suggested that in teenage girls, more stringent criteria are required:

• BOTH of the following
  • Oligomenorrhoea or amenorrhoea at least 2 years after menarche
  • Clinical and biochemical hyperandrogenism
• Absence of an alternative cause (e.g. Cushing’s, congenital adrenal hyperplasia)

Differential Diagnosis

• Hypothyroidism
• Hyperprolactinaemia
• Cushing’s syndrome
  • Consider dexamethasone suppression test or 24-hour urinary cortisol as screening
• Acromegaly
• Androgen secreting ovarian or adrenal tumour
  • Symptoms likely to be more severe than hirsutism seen in PCOS, often have a quicker onset and may include; testosterone >5 mol/L, clitoromegaly, deepening voice, increased musculature, male pattern balding

Investigations

• ↑ LH
  • May be normal
• FSH
  • If both LH and FSH are raised – more likely ovarian insufficiency
  • If both are low – consider hypogonadotrophic hypogonadism
• ↓ E2 (estradiol)
• ↑ or  Testosterone
  • Often only slightly raised. If >5nmol/L need to exclude an androgen secreting tumour
• ↓ SHBG (sex hormon binding globulin)
• ↑ Prolactin
• ↑ oestrogen – which ultimately results in increased risk of endometrial hyperplasia / endometrial cancer
• TFTs – for hyperthyroidism, which may mimic PCOS through amenorrhoea and weight gain:
  • ↑T4
  • ↓TSH
• Fasting glucose and / or oral glucose tolerance test
  • Checks for presence of insulin resistance

USS

• Shows >5 follicles per ovary
  • Despite the name, they are not true “cysts”!
• Sometimes said to look like a string of pearls
• Scans in women under the age of 20 (or <8 years of ovulation) should be interpreted with caution as physiologically they often have follicles / cysts visible

Examination

• May show excessive cervical mucus – consistent with excess oestrogen
• Signs of hirsutism (male pattern facial hair, acne)

Risks / complications

• Insulin resistance and possibly later, Type II diabetes
• Cardiovascular disease
  • Including MI and stroke
• Hypertension
• Dyslipiaemia – disorders of lipid metabolism
• Weight gain
• Miscarriage
• Autoimmune thyroid disease
• Acanothosis nigricans – patches of dark skin, typically under the arms and on the back of the neck
• Increased risk of endometrial cancer due to unopposed oestrogens.
  • Particularly if periods are <3 monthly
  • This is why when the oral contraceptive pill is recommended – it is recommended to have a withdrawal bleed at least once every 3 months

Management

PCOS is a lifelong condition. Early diagnosis and treatment minimises the risks of complications and improves quality of life. In particular, warn about the risks of diabetes and increased cardiovascular disease risk.

There is no cure. In particular, lifestyle factors should be emphasised.

• Weight loss
  • For all patients with BMI >25, weight loss will improve symptoms
  • Patients should aim for a weight loss of 5%
  • This may induce normal menstrual cycles and alleviate the need for hormonal and other medical treatments
• Advise increased exercise to all patients
  • Proven to improve psychological symptoms, metabolic features, pregnancy rates and anovulation – even regardless of weight loss
  • Aim for 150 minutes of moderate intensity exercise (brisk walk or equivalent) per week – e.g. 5×30 minutes
• Avoid or cease smoking
• Offer screening for T2DM
  • Treat if present – e.g. with metformin
• Ask about sleep apnoea symptoms and test if indicated
• Treat hypertension if present
• Treat hyperlipidaemia if present
  • No evidence for use of statins if cholesterol is normal. Same guidelines as for general population
• Oral contraceptives – combined hormonal contraceptive (CHC) is the hormonal treatment of choice. They reduce the androgenic symptoms, as well as reduce endometrial cancer risk. Usually recommended to have 3-monthly withdrawal bleeds.
  • Be wary of contraindications in patients with increased BMI
    • BMI >40 – contraindicated
    • BMI 35 to 39 – benefits outweigh risks if no other risk factors
    • BMI 30 to 34 – benefits outweigh risks if also one other risk factor present
  • If withdrawal bleeds do not occur when they should, USS of the endometrium should be performed. If endometrial thickness is >7mm, refer for biopsy
• Metformin may be helpful to treat insulin resistance, even if T2DM is not present. It can not only improve diabetic symptoms, but can also help menstrual problems (amenorrhoea / oligomenorrhoea), and can help ovulation
  • Metformin is recommended by NICE in those trying to conceive, but otherwise has been shown to be inferior to hormonal contraceptive pill to treat other symptoms of PCOS. As such, NICE recommends that it not be used unless to treat T2DM, or for fertility.

Treatment of hirsutism – if a problem, consider cosmetic treatments (hair removal) or an anti-androgen e.g. cyproterone (an anti-androgen prednisolone – which is available in some CHC preparations).

• Cyproterone has been shown to be no more effective than CHC at controlling androgenic symptoms. It is also usually only initiated by a gynaecologist (not by GP)
• Spironolactone and finasteride – are antiandrogenic alternatives, but also teratogenic, so avoid pregnancy! They should be used with an additional form of contraception. Can be initiated by a GP.
  • e.g. spironolactone 100mg daily
  • Check potassium once month after starting spironolactone
  • If not effective after 6 months, consider combining with a CHC

Fertility Advice

The risk of infertility increases with age, particularly after the age of 30. Advise patients to consider starting a family as early as practicable. Lifestyle factors (particularly weight loss) improve fertility.

• Metformin – has been shown to improve fertility in women with a BMI <30. Evidence is less clear in patients with BMI >30
  • Evidence is not conclusive
  • It improve pregnancy rates, but has not been conclusively shown to improve live birth rates. 
• Refer to specialist if unable to conceive despite the above advice and treatment
• Clomifene – usually used in conjunction with metformin, will help ovulation.
  • Induces ovulation
  • Increases the riks of multiple pregnancy and ovarian cancer
  • Monitor effect with USS in at least the first cycle
  • Should not be used for more than 6 months
  • Usually used in conjunction with metformin
• Ovarian drilling – is recommended as second line if clomiphene is not working. Helps to reduce steroid production.

Also be aware that there is a higher incidence of gestational diabetes in women with PCOS (thought to be >2x risk), as well as increased risk of premature birth, and pre-eclampsia.

Flashcard

References

• Polycystic Ovary Syndrome – patient.info
• PCOS – HealthPathways
• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.

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Postcoital bleeding refers to vaginal bleeding (or spotting) that occurs after sexual intercourse, and is not related to menstruation. It is important to consider cervical cancer as possible cause, although it is rare.

• It occurs in about 5% of the general population at any given time
• About 1/3 of patients will also have intermenstrual bleeding
• Cervical cancer accounts for about 1 in 5000 cases of post coital bleeding (lower risk in younger populations and higher risk in older populations)

Bleeding may be reproducible upon examination of the cervix.

Causes

• Risk factors – ask about partners (number of partners, protection, Hx of sexually transmitted infection etc)
• Ask about other symptoms – discharge, pain

Cervical Ectropion

• An ectropion occurs when the columnar epithelium of the cervix is exposed to the vaginal vault
• Typically causes vaginal discharge, but occasionally associated with bleeding
• Common in women taking the combined hormonal contraceptive pill

Cervicitis

• Inflammation of the cervix
• A sign rather than a true diagnosis
• Has multiple causes:
  • Chlamydia (most common)
  • Bacterial Vaginosis
  • Other infective causes
• Cervix may appear generally red and inflamed on examination and bleeding may be reproduced when the cervix is touched

Cervical / endometrial polyps

• Benign
• May be palpable on bimanual
• Likely visible on speculum
• Patient may be able to feel an unusual sensation when polyps are present
• On examination – smooth red/purple growths that arise from the os. Usually painless, and can be easily removed.

Vaginal Cancer

• Likely to be older populations

Cervical Cancer

• Likely to be an older patient, but may be as young as mid/late twenties
• Ask about smears
• May cause bloody discharge
• On examination – often a firm lump that will exhibit contact bleeding

Other uterine malignancies

• Rarely cause post-coital bleeding, and in cases where they do, there is often also intermenstrual bleeding

Rare causes:

• Endometriosis
• Fibroids
• Genital prolapse

History Taking

• Where is the bleeding coming from? – might seem a silly question, but sometimes it may be coming from the rectum or the urinary system. Bleeding may even be coming from the male sperm. Any doubt can be solved by using a condom to rule out haematospermia, and / or a tampon at the time of bleeding to asses to location.
• Periods – normal? Heavy? Absent? Any change recently? Any intermenstrual bleeding?
  • These questions help to differentiate a cervical cause from an intrauterine cause.
• Contraception – what is she using?
• Any symptoms of infection? – Any vaginal discharge? Pain (dyspareunia – pain during intercourse), dysuria, recent change of sexual partner?
• When was the last cervical screening test and what was the result?

Examination

• Examine the cervix as part of a speculum examination
• Polyps, ectropion, cervicitis, prolapse and cervical cancer may all be visible

Investigation

• Cervical smear test and HPV testing should be performed
• High vaginal swabs for infection (chlamydia and gonorrhoea) – especially if there is any vaginal discharge in the history or cervical discharge seen on examination, or if there are any risk factors for STI
• Biopsy – of the cervix maybe performed if any abnormal lesions are identified
• Colposcopy should be performed for any woman with persistent post-coital bleeding without an identified cause from previous examination and investigation

Management

Treat the cause

• Infection – treat the infection identified
• Ectropion – does not require any specific treatment
• Polyps – can be removed – simply by twisting at the base and pulling the polyp off. Cauterising the base may reduce the risk of recurrence and post procedure bleeding
• CIN – manage as per CIN / cervical cancer guidelines

In many cases, symptoms resolve spontaneously.

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Postcoital bleeding – uptodate

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• Term baby – between 37 – 41 weeks
• Pre-term baby – before 37 weeks
• Post term baby – after 42 weeks
• Neonate – <28 days old
• Stillbirth – dead baby delivered after 24 weeks
• Perinatal mortality – stillbirths + deaths within first week of life
• Neonatal mortality – deaths between 1-4 weeks
• Low birthweight – <2500g
• Very low birthweight- <1500g
• Extremely low birthweight – <1000g
• Small for age – <10^th centile
• Large for age – >90^th centile

Newborn

• Routine examination of the newborn
• Hearing tests

Examination

• Weight, length, head circumference (all plotted)

Health promotion / advice

• Offer BCG and hep B vaccination if at risk
  • Hep B vaccination should be repeated at 1, 2 and 12 months
• Feeding and nutrition advice
• Preventing SIDS – avoid overheating, cessation of parental smoking

5-6 days old

• Screening
  • Midwife will perform the Guthrie test
  • Detects raised levels of the amino acid phenylalanine; which indicates metabolic disease

12 days old

• Midwife visits to check general baby and family wellbeing (both physical and mental needs, chance to ask any questions)

8 weeks

• Screening
  • The GP performs screening – pretty much identical to the new baby screening test
• Immunisations – 2 jabs:
  • [Diphtheria + tetanus +pertussis] + [polio] + [HiB]
  • Pneumococcus
• Examination
  • Length, weight, head circumference
  • Ask parents about vision / hearing
•  General
  • Any parental concerns?

3 Months

• Immunisations – 2 jabs:
  • [Diphtheria + tetanus +pertussis] + [polio] + [HiB]
  • Men C
• Examination
  • Length, weight, head circumference
  • Ask parents about vision / hearing
• General
  • Any parental concerns?
  • Discussion about weaning (should begin at about 6 months)

4 Months

• Immunisations – 3 jabs:
  • [Diphtheria + tetanus +pertussis] + [polio] + [HiB]
  • Men C
  • Pneumococcus
• Examination
  • Length, weight, head circumference
  • Ask parents about vision / hearing
• General
  • Any parental concerns?

8 months

• Screening
  • Health visit team will asses child’s development (physical, emotional, social)
  • If parents worried, hearing and vision will also be assessed.
• General
  • Any parental concerns?
• Examination
  • Length, weight, head circumference
  • Ask parents about vision / hearing

12 Months

• Immunisations – 1 jab
  • [HiB + Men C]
• General
  • Any parental concerns?
  • Discussion about weaning
• Examination
  • Length, weight, head circumference
  • Ask parents about vision / hearing

13 Months

• Immunisations – 1 jab
  • MMR
• General
  • Any parental concerns?
• Examination
  • Length, weight, head circumference
  • Ask parents about vision / hearing

2-3 years

• Examination
  • If indicated, the health visiting team can visit to check development

3 years 4 months

• Immunisations – 2 jabs
  • MMR
  • [Diphtheria + Tetanus + Pertussis] + [Polio]
• General
  • Any parental concerns?
• Examination
  • Height, weight, head circumference
  • Ask parents about vision / hearing

4-5 years (preschool)

• Screening
  • Orthoptists for visual problems
• General
  • Any parental concerns?
• Examination
  • Height, weight, head circumference
  • Ask parents about vision / hearing

5 years (school entry)

• Screening
  • Vision
  • Hearing
• General
  • Any parental concerns?
• Examination
  • Height, weight, head circumference
  • Furthur examination only if parental concerns

Girls 12-12

• Immunisations
  • HPV

Age 13-18

• Immunisations – 2 jabs
  • Diphtheria + Tetanus
  • Polio

References

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• Both oestrogen and progesterone are produced from cholesterol
• LH and FSH are known as the gonadotropins
• GnRH is released in a pulsatile fashion. These pulses last 5-25 minutes, and occur every 1-2 hours. They result in the pulsatile release of LH and FSH. When GnRH is produced continuously, its ability to cause the release of LH and FSH is lost. GnRH release is:
  • Low in childhood, and activated during puberty
  • Controlled by feedback loops of oestrogen (stimulated GnRH) and progesterone (inhibits GnRH)
  • Suppressed in pregnancy by prolactin
  • Disrupted in Polycystic ovary syndrome
  • Affected by hypothalamic-pituitary disease – e.g. space occupying lesion, trauma.

 

Phases

Follicular phase

• The normal ovary contains many primary follicles – these have the potential to become ovum under the correct stimulation. They contain a large, central oocyte, surrounded by several small follicular cells.
• During the follicular phase, under the stimulation of FSH, up to 20 primary follicles are stimulated to grow. They become secondary follicles. They are essentially in a race to become the next ovum. As they grow, the number of follicular cells increases rapidly, and the follicular cells differentiate to become Granulosa Cells.
• By day five of the cycle, one of the follicles emerges as the dominant follicle, aka the Graafian , or Tertiary follicle. During days 6-14 this follicle grows rapidly in response to FSH. During this time it will release Oestrogen, which will act as a positive feedback loop, by stimulating the production of more GnRH, as well as accounting for secondary sex characteristics, and having important effects on muscle and bone metabolism.
• Now stimulated by a rise in LH, this is stimulated to complete its suspended state of meiosis I, and in doing so the oocyte splits in two, releasing one large cell, and one small polar body. This continues meiosis as far as metaphase II, which is not completed until fertilisation.
• Then, the oocyte is released from the ovum, and into the fallopian tube. This is the start of the luteal phase

Luteal Phase

• The empty follicle remains in the ovary, as becomes the corpus luteum. Under stimulation of LH this will slowly secrete progesterone, in increasing amounts for 7 days, after which time is begins to degrade, and progesterone output falls.
• Progesterone is responsible for the build up and maintenance of the endometrium. In the absence of progesterone, the lining will die and slough off (menses).
• In the absence of fertilisation – The corpus luteum will produce progesterone and oestrogen for 14 days, as it slowly degrades.
  • The corpus luteum never completely disappears. It remains in the ovary as the corupus albicans, which is essentially just a mass of fibrous scar tissue. In older women, the build up of these bodies can cause misshaped ovaries.
• In the presence of fertilisation – the implanted embryo will produce hCG (Human chorionic gonadotropin). This stimulates the corpus luteum to continue producing progesterone, to maintain the endometrium. At this stage, the corpus luteum is called the corpus luteum graviditatis
  • Eventually, the placenta will take over the production of progesterone, once it becomes large enough.  

 

• In menses- between 35-80ml of blood is lost
• It typically lasts 3-5 days
• The highest rate of fertility (the time when sex is most likely to result in pregnancy) is from 5 days before ovulation to 2 days after ovulation.
  • In a normal 28 day cycle, with a 14 day luteal phase, this is roughly 5-12 days after the end of menses.
• Note the two peaks of Oestrogen:
  • The first is the production of oestrogen by the tertiary follicle, and its main role is to prepare the endometrium for implantation
  • The second is the production of oestrogen by the corpus luteum.
• Oestrogen inhibits the anterior pituitary release of FSH and LH – and this effect is exaggerated in the presence of progesterone (i.e. more exaggerated in the second half of the cycle).
• Inhibin also has a large inhibitory effect, particularly on FSH release.
• Endometrium – the growth of the endometrium and swelling of individuals cells occurs to provide enough nutrients to a developing fetus. In the cells there are high levels of lipids, proteins and glycogen as well as other nutrients that an embryo will need.
  • After implantation, the decidua (the endometrial cells) will provide all nutrition for the first 16 days, and will continue to supply some nutrition until about the 16^th week, when the placenta is developed enough to take on the role fully.

Explanation of the cycle

• After Ovulation – days 15-28 – the corpus luteum is secreting lots of progesterone, oestrogen and inhibin. This keeps levels of FSH and LH low. As corpus luteum output falls, FSH and LH levels rise, reducing inhibition of the anterior pituitary;  leading to the start of the next cycle, and the activation of several primary follicles to begin development.
• Days 1-11 – FSH and LH production gradually fall, as they stimulate the follicles to produce oestrogen, which inhibits FSH and LH production.
• Days 12-14 – The excessively high level of oestrogen stimulate the production of very high levels of FSH and LH, as the negative feedback loops is reversed. This causes ovulation, and results in the creation of the corpus luteum.
  • Sometimes, the LH surge is not great enough to cause ovulation – these cycles are known as ‘anovulatory’. These typically occur during puberty, as the reproductive system matures, and also occur just before the menopause. In these cases, no ovum is released, and although the cycle will continue, it is shortened, and there is no production of the corpus luteum, and no production of oestrogen and progesterone in the second phase of the cycle.

More about the hormones

FSH – follicle stimulating hormone

FSH is produced by the anterior pituitary gland. Its release is affected by GnRH pulses.

It has several effects in both males and females including development, growth and puberty. In men in is also related to the production of sperm, and in women, in combination with LH, it helps to regulate the menstrual cycle and cause ovulation. In particular it helps to select the most mature follicle to advance to ovulation.

In women, the level of FSH varies depending on the timing of the cycle. In men, FSH levels remain steady after puberty.

• Testing levels of FSH is occasionally used to diagnose menopause
• In most cases – menopause is a clinical diagnosis (i.e. diagnosed without the use of tests)
• However ins one cases – typically those where early menopause is suspected (e.g. less Thant he age of 40 with no periods for >1 year) then FSH levels may be tested
• FSH levels that are consistently raised can be used to confirm the diagnosis of early menopause. Typically this requires two tests that are 4-6 weeks apart

References

• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Beers, MH., Porter RS., Jones, TV., Kaplan JL., Berkwits, M. The Merck Manual of Diagnosis and Therapy

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• the most common benign breast lump
• can occur from any age after puberty
  • most common in the third decade
• Usually unifocal, but can be multiple.

Pathology

• Made up of both connective and glandular tissue
• They are usually subject to the same cyclical changes as the other glandular breast tissue – e.g. they may be more tender at a particular time of the month.
• They will grow rapidly in pregnancy as a result of hormonal changes

Presentation

• Usually well defined borders, but lobulated and lumpy on palpation
• Usually 10-40mm in size, but can be larger
• Mobile – old fashioned nick-name – breast mouse
• They have no potential to become malignant – although sometimes, a constituent part of a breast carcinoma can be a fibroadenoma.

Juvenille Fibroadenoma

• Due to their rapid growth, they may be confused with phyllodes tumour – a malignant breast neoplasm, accounting for 1% of cases of breast cancer. However, it is rare in young women.

Duct Papilloma

• The most common cause of nipple discharge
• Less common that fibroadenomas
• Tend to occur in middle aged women, but can be seen in younger and older patients
• Usually solitary
• Rise from ductal epithelium
• They are not a form of pre-malignancy

Presentation

• 80% of patients will have a bloody nipple discharge.
• Most will have a palpable mass. This will typically feel like an elongated mass – along the lumen of a duct. They can also be more spherical in shape, in which case, the duct lumen will be enlarged.
• Usually found within 40mm of the nipple, due to their ductal nature.

Adenomas

• Rare
• Tubular Adenomas
  • 10-40mm diameter, most common in the third decade
• Lactating Adenomas
  • These are tubular adenomas which may begin secreting during pregnancy
• Nipple adenomas – a solitary nodule under the nipple, can occur at any age. May ulcerate and be mistaken for Paget’s disease of the nipple, and may cause a bloody discharge. Well defined borders.

Cysts

• Often cause discomfort
• May result in epithelial hyperplasia – which increases the risk of cancer
• Can cause large palpable lumps, which may cause worry
• Used to be called chronic mastitis – but this is a misnomer, as there is no inflammation involved, and this term should no longer be used.
• Most common in those aged 40-45, but also relatively common in 30-40 year olds

Epidemiology

• 10% of women will present with a cyst at some stage
  • Post mortem analysis shows that 50% of women have some features of fibrocystic change
• Most common in the 4^th and 5^th decades of life, and do not tend to occur or persist after the menopause, as they are caused by hormonal effects on ductal and lobular epithelium.
  • They may persist after the menopause in those taking HRT
  • Most common just before the menopause

Aetiology

• Basically unknown. Hormonal role.
• More common as you approach menopause

Pathology

• Cyst formation in other organs is usually due to blockage of some sort of duct or lumen, however, this is not the case in fibrocystic change.
• The cysts form as a result of some sort of hormone imbalance, which results in epithelial hyperplasia and duct/lobular dilation, allowing a fluid-filled cavity to form.

Presentation

• A cysts is essentially a fluid-filled sac in the breast.
• The breast lumps are well circumscribed, and depending on the size, will feel like a grape, or water-balloon in the breast tissue. They are usually firm but not hard, and mobile. The size of the lump may vary with the menstrual cycle, with the lump larger before menstruation, and smaller after menstruation
• Pain – may be cyclical, and is typically worse during:
  • The second half of the menstrual cycle
  • Pregnancy
• The lump may be visible on inspection
• Often several may co-exist at once, although there are many cases where only one cyst is present.

Investigation

• Palpation – described above
• Imaging – usually mammogram, or USS, or both. USS is more sensitive to cystic changes, and the cyst will usually appear dark on the scan. USS is also useful for guided biopsy e.g. in the case of breast implants
• Cytology – FNA – fine needle aspiration. It is relatively easy to take a fluid sample, but you should be wary of sticking a needle in if there is a history of past surgery, particularly breast implant. The fluid is typically brown / green and watery in consistency. It is best practice to send the sample for cytology, particularly if the fluid does not fit this description (e.g. blood, pus). If the fluid appears normal, and there is not a history of cysts, then the likelihood of any significant problem is very low, and the fluid does not need to be tested. Advise the patient to seek further help if any lumps recur.
  • The FNA is also often therapeutic, as it removes the fluid, and the lump subsides.

Treatment

• The fluid volume can be anywhere from a couple of ml, to 60ml. Those less than 5ml will usually not be symptomatic, and in many cases, larger ones may not be a problem.
• Aspirated cysts may recur, in which case, similar treatment can be employed. You should have a higher level of suspicion to send the sample off to the lab in recurrent cases.

References

Read more about our sources

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Presentations of Breast Disease

• Lump
• Pain – Rare in breast cancer
• Asymmetry – Change in breast size – particularly related to the menstrual cycle
• Change in breast feature
• Change in Nipple
• May present to clinic due to strong FH of breast disease

Breast lumps

Examination

• Get a CHAPERONE!
• Careful of your terminology – try to use phrases like ‘I will examine the left breast now’ and not things like ‘I will have a feel of the breast now’

Explanation

Inspection

• Peau d’orange – ‘orange peel skin’ – part of the skin of the breast may have a texture like orange peel. This is often a sign of cancer.
• Tethering – a dimple in the skin often indicates an underlying mass (usually cancer) pulling on the skin
• Rash / redness

Any visible lumps
Check symmetry

• Breasts are not usually completely symmetrical. If there is a gross abnormality, you can always ask the patient when she first noticed, and if it has been there very long.

Now ask the patient to put her hands on her hips and squeeze inwards – this tenses the pectoral muscles, and can bring out any lumps or abnormalities
Now ask the patient to put her hands behind her head –similar to the above, can allow you to see lumps and other abnormalities that may not have been visible before. Also allows you to look into the axilla.

Any other abnormalities

• Don’t forget to look right along the tail of the breast up into the axilla.
• Don’t forget to look under the breast. You may need to life up the breast to see properly into the skin fold underneath

Palpation

• You should have a system. Some doctors will divide the breast into quadrants, and check each quadrant individually, but a better way is to image the breast like a clockface and move round clockwise. You can then also note any abnormalities by their relation to the clockface, e.g.: ‘A 1-2cm, hard lump, tethered to the skin at 4’o’clock in the left breast.’
• Technique – you should NOT your fingertips or your palms, instead, use the ‘pad’ of your fingers, basically, the part of the finger under the middle phalange, and the DIP. Use several finger at once, and start at the outside of the breast and move inwards toward the nipple.
• If you find a lump, continue the rest of the examination of the particular breast, and then come back to it at the end, and fully analyse it then. Norma breast tissue can be a bit lumpy, especially in the ‘tail’ of the breast (12 to 3 o’clock region). Some doctors describe it as like feeling for a marble in a bag of rice!
• Remember to feel behind the nipple – tell the patient what you are about to do before you do it!
• Repeat for the other breast
• Some doctors then recommend you repeat the examination with the patient sitting. Different position can expose lumps that you didn’t previously feel.

Lymph node exam

• Support the weight of the woman’s arm, with your own, and ask her to relax.
• It may feel uncomfortable, but shouldn’t be painful
• Not palpate for lymph nodes in the axilla. Make sure you feel all the four sides of the axilla
• Palpable lymph nodes can again be normal – e.g. with general arm trauma / cuts / bruises, but in these cases, the inflamed nodes should subside within a couple of months. They may of course also be a sign of breast pathology (e.g. cancer)

Presenting findings

• Size
• Location
• Shape
• Surface
• Texture
• Mobility

Triple assessment and grading of the lump

• Examination
• Fine need aspiration (Cytology)
• Imaging (can be Mammography – if patient >35 , USS if patient <35, or MRI if USS/mammogram is not definitaive)
• Any patient referred to hospital for a breast problem will have a triple assessment to try to find the underlying cause.

Examination

• E1 – Normal (no lump)
• E2 – Benign lump
• E3 – A lump
• E4 – A suspicious lump
• E5 – Probable cancer

Cytology

• C1 – inadequate sample
• C2 –Benign
• C3 – Atypical features, but still likely benign
• C4 –Atypical features, probably malignant
• C5 –Malignant

Imaging (<35 USS [breast tissue too dense for mamm.], >35 Mammogram)

• M1 / U1 – Normal
• M2 / U2 –benign
• M3 / U3 –Probably benign
• M4 / U4 –Probably malignant
• M5 / U5 –Malignant

The post Breast Examination appeared first on almostadoctor.

Breast cancer is the most common cancer in women, and the second most common cause of death from cancer, after lung cancer.

There are more published studies (on PubMed) on breast cancer, than on any other disease.

Breast cancer is broadly classified as:

• Ductal – tumours arising from the epithelial lining of the ducts
  • This is by far the most common type
• Lobular – tumours arising from the epithelial lining of the terminal ducts of the lobules

Breast cancers can also be classified as invasive or in situ. Most breast cancers are invasive – and therefore more dangerous.

Epidemiology

In the UK, a woman has a 1/9 chance of developing breast cancer

• Incidence about 95 per 100 000
• Mortality of about 23 per 100 000
• Has a mortality rate of about 25%
  • Mortality rate is decreasing due to earlier diagnosis (from screening) and improved treatments
  • Mortality rate is typically higher than many other cancers because breast cancer often presents late. It often does not cause any symptoms until it has spread to other tissues
• About 5% are metastatic at the time of diagnosis

It is the most common cause of death in women aged 35-55

• In some developed countries (e.g. Australia) it is the most common cancer in women. In others, it is a close second to lung cancer
• Incidence increases with age
  • <5% of cases in women <35
  • 25% in women <50
  • The remaining 70+% of cases are in women aged >50

It is responsible for 20% of all cancer in women

Aetiology

Risk increases with age
Oestrogen exposure – long, uninterrupted periods
Large gap between menarche and menopause

• Early first period
• Late menopause
  • Women with 40 years of active menstruation have 2x the risk of those with 30 years
• Nulliparity
• First pregnancy  at age >30 years
• HRT
  • HRT with oestrogen only – little to no increased risk
  • HRT with oestrogen and progestogen increases the risk of breast cancer
  • Increased risk is related to the period of use of HRT. Risk reduces after HRT is stopped. Risk if <5 years of HRT is thought to be minimal.
• The Pill
  • Risk thought to be very low
  • Correlated to the age at which the pill is ceased (older age = greater risk) rather than the duration of use of the pill
  • 10 years after ceasing the pill the risk has returned to baseline
• Not breast-feeding
• Radiation to the chest
• Obesity / high fat diet / alcohol
  • Increases the risk particularly in those over 60
• Breast augmentation is NOT correlated with an increased risk of breast cancer

Family history

• BRCA1 and BRCA2 genes
  • Account for about 5% of breast cancers
• BRCA1:
  • Mutation on chromosome 17
  • Lifetime risk of breast cancer is about 75%
  • Lifetime risk of ovarian cancer is about 50%
  • Men with the gene also at increased risk
• BRCA2:
  • Mutation on chromosome 13
  • Lifetime risk of breast cancer 40-85%
  • Lifetime risk of ovarian cancer <25%
  • Lifetime risk of breast cancer for men is about 6%

Atypical epithelial hyperplasia
Geographical variation

• Highest incidence in the ‘Western World’ i.e. North America, Europe, Australia, NZ. Incidence is lowest in Africa and South-East Asia
• These variation are probably the result of the other above risk factors, e.g. in these western countries, menarche is likely to be earlier, first pregnancy likely to be later, diets high in processed foods, alcohol intake and post menopausal weight likely to be greater.

Genetics

BRCA1 – on chromosome 17, accounts for around 50% of familial cases that appear to be inherited in an autosomal dominant fashion.

• 60-85% lifetime risk of breast cancer.
• Also increased risk of bowel cancer, ovarian cancer (50% lifetime risk) and prostatic cancer (men)

BRCA2 – on chromosome 13 – less common than BRCA1, accounts for 30-40% of familial cases.

• Similar lifetime risk to BRCA1
• Increased risk of ovarian cancer (25% lifetime risk), but lower risk of other cancers compared to risk of other cancers from BRCA1
• Men with BRCA2 have a 6% chance of developing breast cancer (100x greater than the normal population)

Both BRCA1 and BRCA2 are tumour suppressor genes, responsible for the production of proteins which help repair damaged DNA during cell reproduction. In the mutated forms of these genes, the protein produced is ineffective, allowing DNA defects to accumulate over time.

• Typically, mutated BRCA1 genes produce a protein that is too short, and is unable to perform the normal repair process.
• There are hundreds of different mutations – but all have the same result
• Most people only have one defective copy and one normal copy
• Those who have two copies of BRCA2 will also have:
  • Fanconi Anaemia – in this condition there is: short stature, skeletal abnormalities, increased incidence of solid tumours and leukaemia, and bone marrow failure.
• There is also an increased risk of ovarian cancer in women with BRCA1 and BRCA2, but the risk is less with BRCA2.

• HER2 mutation occurs in about 20% of breast cancers
• It is associated with a worse prognostic outcome
• Has specific treatment in the form of the monoclonal antibody Trastuzumab (Herceptin). This will bind to the receptor, and cause the production of p27 within the cell, which reduces cell proliferation
• As a result of this specific treatment, breast cancers are routinely tested for HER2/neu presence.
  • HER2 expression is reduced by the presence of oestrogen. In some tumours treated with tamoxifen, HER2 expression can increase.

Presentation

• Discharge
• Nipple changes
• Skin tethering or dimpling
• Tethering to underlying tissues, e.g. muscle
• Ulceration (late sign)
• Oedema / erythema
• Paget’s disease of the nipple
  • A complication of ductal carcinomas
  • Causes itching, redness, crusting and discharge from the nipple
  • Accounts for about 1% of cases of breast cancer

• Most commonly seen in the upper, outer segment

Screening

UK

Originally set up in 1988. Costs £75m per year (roughly £45 per woman screened, or £37 per woman invited).
The programme is run on a three yearly rotation basis depending on the GP practice, which means the first invitation for screening will be received any time after the woman’s 50^th birthday, but before the 53^rd.
After a woman reaches the upper age limit (70), then invitations are not routinely sent, but women are still encouraged to and entitled to make their own NHS appointments if they wish.

It is estimated that the screening program saves around 1400 lives per year (or 1 in every 500 women screened). This is roughly a 35% reduction in mortality when compared to a non-screened population.
Screening is also available for women under 50 who:

• Have had a previous cancer
• Have had a first degree relative with cancer <50 years
• Have a known BRCA1, BRCA2 or TP53 gene

Australia

• Is typically performed every 2 years
• Offered to all women aged 50-74
• Should be offered to women aged 40-49 with:
  • Moderately increased risk (see below)
• Consider screening every year in people with moderately increased risk

Moderately increased risk

Affects about 4% of the population. Defined as:

• x1 first degree relative with a breast cancer diagnosis at age <50
• >1 first degree relative with breast cancer diagnosis at any age

Potentially High risk

Affects about 1% of the population. Defined as:

• Women with TWO 1st OR 2nd degree relatives with BREAST or OVARIAN cancer PLUS at least one of the following:
  • >2 relatives affected
  • Breast cancer diagnosed at <40 years
  • Bilateral breast cancer
  • Breast and ovarian cancer in the same woman
  • Jewish ancestry
  • Breast cancer in a male relative
• One 1st or 2nd degree relative with breast cancer diagnosis at <45 years PLUS relative on same side of family with sarcoma at age <45
• Family member with known high risk breast cancer gene (BRCA1 or BRCA 2)

The procedure

Mammography – an x-ray of the breast tissue. Usually anteroposterior and lateral images of the breast are taken.

• Sensitivity – 75-95%
• Specificity – 95%
• It is not effective at detecting the early changes of breast cancer in women <35 years – as the breast tissue in women of this age is more dense, and thus the subtle density changes of early dysplasia cannot be seen. USS is used to assess breast lumps in women <35

• It is usually a bit uncomfortable, and in some women it may cause pain. One study suggests that good explanation of the procedure beforehand reduces the perception of pain. Taking aspirin or paracetomol before the procedure does not alter the perception of pain.
• Sometimes products on the skin (e.g. deodorant, talcum powder) may appear as calcifications.
• Results usually available within 1-2 weeks, but can take up to 4.
• 5% (1 in 20) screened women are called back for further review – but only about 13% of these (or, about 0.65% of the total) will actually have cancer. So, for every 8 women called back for review, only 1 of them will have cancer.

Digital Mammography – FFDM – Full field digital mammography –  a newer technique, that provides higher resolution imaging, and in theory is more sensitive in younger women with more dense breast tissue. However, in trials, FFDM has not been shown to be any more effective at detecting cancer than traditional mammography, and it is not routinely used.
MRI – MRI scanning is recommended by NICE for some women with a very high risk (e.g. known gene defects), as it is more sensitive, but much more expensive.

Pathology

• Most of the breast is made of adipose (fatty) tissue
• Coopers ligaments attach at one end to the underlying pectoral muscles, ad at the other end, to the skin, and help support the breast
• Glandular tissue is grouped into lobules
  • Within these lobules are alveoli – sore of like modified sweat glands that make mild instead of sweat

• The glandular tissue respond to several hormones
  • Oestrogen
  • Progesterone
  • Prolactin
  • In response to these hormones, the alveolar cells divide and the lobules enlarge
  • Without these hormones, the cells undergo programmed cell death (apoptosis)
  • As such, every menstrual cycle, the alveolar cells go through a period of division and then apoptosis
  • Every time a cell divides, there is a chance of a mutation that can lead to a tumour formation
  • Thus – factors that increase the number of menstrual cycles in a woman lifetime increase the risk e.g. early menarche, late menopause
  • Also, this is why medications containing oestrogen increase the risk
• At the menopause, the breast tissue will involute. During this process, much of the glandular tissue dies (undergoes apoptosis), and is replaced by fat.  The general density of the breast reduces.
  • This is in response to the lack of oestrogen
  • The average age of the menopause in UK women is 50

• A single mutated epithelial (duct) cell will start to replicate out of control

Tumour confined to the ducts, or the acini of the lobules, and there is no infiltration of the basement membrane. Although described as non-invasive, these tumours have the potential to become invasive, and all invasive carcinomas will have at some time been non-invasive.

Non-invasive carcinomas therefore, are a stage of pre-malignancy, although not all non-invasive carcinomas will become malignant.

Can be:

Ductal carcinoma in situ

• Occur in both premenopausal and post-menopausal women. Usually patients are 40-60 years of age. May be extensive, and associated with fibrosis, in which case it will be a large palpable mass.
• Defined as a cancer that has not spread beyond the basement membrane of the ducts
• If large ducts are involved, it is associated with nipple discharge
• May present as Paget’s Disease of the nipple
  • In these cases, the initial tumour will have originated in one of the ducts, but at some stage, a cancerous cell will have migrated down the duct and become attached to the epithelial skin on the outside of the nipple
• Accounts for 5% of breast cancers at presentation – often breast cancer presents later in the invasive phase.
• Typically 10-100mm in diameter and unilateral/unifocal
• Histologically typically occur in small and medium sized ducts
• Lesions may have a solid centre, or a necrotic centre, which can subsequently calcify, making the lesions visible on mammography
• Spread locally along the ducts
• Have a risk of 30-50% of becoming invasive
• If completely excised, prognosis is excellent

Lobular carcinoma in situ

• Usually occur in pre-menopausal women
• Occurs in the lobules and don’t affect the ducts
• Very difficult to detect – as it does not present as a lump, or cause many other signs.
• Often multifocal and bilateral
• No specific features on mammography
• 25-30% of cases will become invasive (i.e. malignant)

Invasive ductal carcinomas

• Account for 75% of all invasive carcinomas
• Occur in both pre and post menopausal women

Invasive lobular carcinoma

• Account for about 10% of invasive carcinomas

Mucinous carcinoma

• Account for 2-3% of invasive carcinomas
• Their borders are not well defined, and they do not cause inversion of the nipple, or tethering of the skin.
• Better prognosis than invasive ductal or lobular carcinomas

Tubular carcinomas

• Cells arrange as tubules
• 1-2% of invasive carcinomas
• Account for a higher proportion of breast cancers detected at screening
• Prognosis is very good

• Rare
• Usually large and well circumscribed
• Histologically show lymphocytic infiltrate and macrophages
• Better prognosis than for invasive ductal carcinomas

Spread

Local – directly into surrounding tissue
Via lymph nodes – in this case typically to the axillary and peri-clavicular nodes

• Sentinel node biopsy is a technique used to asses lymph node spread, without the need for dissection and biopsy of many nodes of the axilla. The sentinel node is the first axillary node along the lymphatic chain – thus all lymph from the breast will drain here first, before moving on through the lymphatic system. However, it is not an anatomical location, as the number and distribution of nodes varies between individuals. To identify the sentinel node a solution containing the radioactive isotope technithium and a blue dye is injected around the nipple/areolar and around the breast cancer itself. Then, a few hours later, the women undergoes surgery of the axilla, and using a hand-held Geiger counter-counter, and by looking which node has turned the deepest shade of blue(!) the surgeon can identify the sentinel lymph node. It removed and sent for histology. Sometimes several nodes may be removed if the spread of dye/isotope is more evenly spread between a few nodes.

Via the blood – to distant sites, in this case, the lungs and bones are most often affected. Other common sites include liver, brain and adrenal glands. The contralateral breast is also often a site of spread.
Unusual characteristics – breast cancers can recur as metastatic disease with / without local disease many years after the removal of the primary tumour. The reason why this occurs in unknown. It could be that the cancerous cells lie dormant, or that there is an alteration in the host immune system many years down the line that results in active disease.

• This can occur up to 20 years after removal of the primary tumour.

Investigations

• Examination
• Fine need aspiration (Cytology)
• Imaging (can be Mammography, MRI or USS)

Examination

• E1 – Normal (no lump)
• E2 – Benign lump
• E3 – A lump
• E4 – A suspicious lump
• E5 – Probable cancer

Cytology

• C1: Inadequate
• C2: Benign
• C3: Atypia, probably benign
• C4: Atypia, probably malignant
• C5: Malignant

Radiology

• R1: Normal
• R2: Benign
• R3: Indeterminate
• R4: Suspicious
• R5: Malignant

Staging and Prognosis

• Young age / premenopausal
• Large primary tumour size
• High grade tumour
• Oestrogen and progesterone receptor negative
• Positive lymph nodes

• Oestrogen acts on nuclear receptors, and controls varies pathways in relation to cell differentiation and growth.

About 50% of tumours have progesterone receptors

• Those with receptor positivity have a greater chance of survival due to treatment methods that can target this mechanism. The fact that the tumour is receptor positive also indicates a higher-level of cell differentiation – which for cancer generally is a good prognostic sign
  • i.e. it hasn’t differentiated to an extent as to become unrecognisable.

• Small (<1cm tumour) with no spread – 90% survival
• Large, high-grade tumour, with >3 nodes involved – 20% survival

• Tumours are also frequently categories by their molecular type, in related to oestrogen, progesterone and HER receptors
• See below in ‘treatment’ for more info

Treatment

Early stage disease

Defined as localised tumours without metastatic spread. Not all of these tumours can be cured with surgery alone.

• 20-30% of breast cancer initially thought to be early stage, localised disease will later recur with metatastatic disease.

• May be a wide local excision or mastectomy. Usually also involves reconstructive surgery.
• Axillary node sampling at the very least (e.g. sentinel node biopsy – above), but usually, axillary node clearance is performed.
• Local excision + radiotherapy – this gives equal survival to surgery, but the risk of recurrence is greater.
• Adjuvant radiotherapy – is given to the chest wall after mastectomy for tumours with a high risk of recurrence
  • Radiotherapy to the axilla – is usually performed if there are +ve nodes on sampling, and node clearance was not performed.
• Side effects of radiotherapy to the chest wall / axilla:
  • Pneumonitis
  • Rib fracture
  • Pericarditis
  • Lymphodema
  • Brachial plexus injury

Advanced Breast Cancer

Advanced breast cancers include locally advanced cancers that cannot be cured with surgery alone, and metastatic breast cancers. Common metastatic sites are bone, brain, lung and liver. 

• Hormone receptor positive is sometimes referred to as HR+, not to be confused with HER2+ !

Suitable for all tumours with oestrogen and/or progesterone receptors – including all HR+ positive tumours, and some HER2+ tumours which are also HR+.The growth of these tumours is restricted or completely prevented by treatments that restrict the tumour access to oestrogen (and / or progesterone).

Oestrogen receptor positive tumours
Treatment aims to decrease oestrogen activity
Tamoxifen is the first line agent

• Given to all women with Oestrogen receptor positive disease for 5 years post op.
• Mechanism – is complicated. It is a selective oestrogen receptor modulator (SERM) – with mixed activity.
• In breast tissue it is an oestrogen receptor antagonist – it binds to oestrogen receptors, preventing oestrogen from doing so, and resulting in a lack of DNA synthesis inside the cancer cells. It is non-steroidal. It causes the affected cell to remain in the G0 /G1 phases of the cell cycle.
• In bone and endometrial tissue it acts as an oestrogen agonist and stimulates the oestrogen receptors. This improves bone density (good – and thus is protective against osteoporosis) but increases the risk of endometrial cancer (bad).
• Tamoxifen is actually a pro-drug – and metabolised into its active agent endoxifen.
• Side effects
  • Fatigue
  • Hot flushes
  • Mood changes
  • Increased risk of endometrial cancer – warn all women prescribed tamoxifen to be watchful of vaginal bleeding and report symptoms immediately.
  • Cardiovascular – Slight increase on the risk of VTE (venous thromboembolism), increased risk of fatty liver
  • CNS – Some evidence to suggest reduced cognition
  • Reduced libido

Aromatase inhibitors  – e.g. letrozole, anastrozole

• Second line agents for oestrogen suppression
• Newer than tamoxifen, and sometimes better tolerated. Again, only suitable for women with oestrogen receptor positive disease.
• Only suitable in post-menopausal women
• Mechanism – aromatase is an enzyme involved in oestrogen synthesis. By inhibiting the enzyme, oestrogen is not synthesised.
• In pre-menopausal women, the majority of oestrogen production occurs in the ovary
• In post-menopausal women, the majority of oestrogen production occurs in the adrenal gland, from the conversion of androgens. Oestrogen is also produced by adipose tissue.
• Aromatse inhibitors inhibit the conversion of androgens to oestrogen in the adrenals – and thus are only suitable as treatment for BC in post-menopausal women.

• Lapatinib – a tyrosine kinase inhibitor given orally. Side effects include diarrhoea, fatigue, nausea, vomiting and rashes
• Cyclin-dependent kinase inhibitors (CKD inhibitors). These are newer agents that show similar efficacy to the above options, and are more effective than endocrine therapy alone.

Chemotherapy

• Often used in conjunction with eh above agents
• Consider the risks vs benefits of any regimen
• Combination regímenes often have a significantly more onerous burden of side effects, and should be avoided in the palliative setting, where quality of life should be prioritised

Triple Negative Tumours

• Chemotherapy is the mainstay of treatment – HR and HER specific treatments are ineffective
• Clinical trials are currently focussing on immunotherapy options

Localised treatment options

• Surgery or radiotherapy may be considered for primary tumours or metastasis that are causing localised issues – for example – a large fungating primary breast tumour, spinal cord compression from bony metastases, or a pleural effusion (which should be drained)
• Brain metastases may be treated with corticosteroids to reduce brain swelling

Bone metastases

• Osteoclast inhibitors – such as zolendronic acid or denostaba (both used in the treatment of osteoporosis) reduce the incidence of pathological fractures and other bone related side effects
• Radiotherapy is often used fro individual bony metastases pain

The MDT

• The multidisciplinary team is an import part of management o the advanced cancer patient – attempting to manage the medical and psychosocial needs of the patient. A typical team might include:
  • Medical oncologist
  • Radiation oncologist
  • Palliative care physician
  • GP
  • Breast cancer nurse
  • Palliative care nurse
  • Psychologist
• It is recommended to involve palliative care services early as they have been shown to improve quality of life

Prognosis

Advanced Brest cancer

• Median survival is 2 years, but is widely variable and depends on the subtype. Median survivals by subtype:
  • HR+ 6 years
  • HER2+ 4-5 years
  • Triple negative 12 months
• Since the mid 1980s 5 year survival has improved from 10% to about 30%
• Herceptin (tratuzumab) has been the most effective new treatment during this period

References

• RACGP – The Red Book – Breast Cancer
• Murtagh’s General Practice. 6th Ed. (2015) John Murtagh, Jill Rosenblatt
• Breast Cancer – Patient.info
• Oxford Handbook of General Practice. 3rd Ed. (2010) Simon, C., Everitt, H., van Drop, F.
• Advanced Breast Cancer – AJGP

Read more about our sources

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