MAMMOGRAPHIC BREAST SCREENING

K Gower ThomasBreast Test Wales

Breast cancer stats

� Commonest female malignancy� UK 2000� 40,707 breast cancers (Wales 2,055 F)� (240 in men) (Wales 16)� Most commonly diagnosed tumour (30% of

all female Ca)

Cancer research UK 2004

Breast cancer

� Many symptoms and signs� lump, thickening, distortion, nipple discharge,

pain, (metastases)� Screen detected cancers usually

asymptomatic, often impalpable

Risks for breast cancer

� Young menarche� Late menopause� No children� Late children� No breast feeding� Obesity� alcohol

� High fatty acids� Lower social class� Little physical activity� No stress!!� FH� HRT� (smoking – no risk)

� Nancy Reagan� Elaine Page� Dusty Springfield� Diana Moran� Olivia Newton John� Anastasia

� Kylie Minogue� Koo Stark� Linda McCartney� Kate Jackson� Caron Keating� Roxanne Blenkin

Biggest risk factors

�� Being femaleBeing female�� Getting olderGetting older� That’s YOU and ME� >1/3 occur after 70y

Middle age – reverse height chart

NHSBSP -The facts

� Began 1988 in UK� Invites 50 -70 every 3 years� Screen 1.3 million pa (25% don’t attend)� Yields 10,000 breast cancers

aims

� To reduce the mortality from breast cancer in the population screened

� Health of the nation target has been met� Currently saves 1400 lives pa

Bone metastases

Fungating carcinoma

screening

� Finds 50% of cancer in the 50- 70 age group (smaller and fewer mastectomies)

� Brings forward diagnosis by 5 years (lead time bias) ??over diagnosis

� The rest occur in women who do not attend screening or as interval cancers these are symptomatic

NHSBSP

� 1988 single view for women 50 – 64y� 50% more cancer registrations now ( half

due to screening and half back ground incidence increase)

� Now 2 view mammography and age extended up to 70y

� older women on request

Screening tool - requirements of a screening programme

� Safe� Easily performed� Acceptable� Specific� Good uptake� Good coverage

� Simple� Reliable� Cost effective� Reproducible� Sensitive

Screening method

� Mammography – film screen� Mammography –digital� Ultrasound� MRI� Clinical examination

Film / screen mammography

� Only method proven in RCT to significantly reduce cancer mortality in 1988

� (MRI has been shown to find more cancers since)

Risks - mammography

� radiation risk� equivalent to flying to Australia, 2 days in NY,� Being a 60 y old man for 20 mins� Inconvenience, anxiety� 1 in 14,000 screened 3x in 10 years will get a

fatal breast cancer

Risks - assessment

� False positive assessment� missing a cancer – false negative � Worry, unnecessary biopsy,� Inconvenience, anxiety� Over diagnosis

Over diagnosis

� Some say up to 30% of screen detected cancers are ‘irrelevant’

� ? conservative estimate� > 10% would not affect woman in her lifetime� Further 10% may be diagnosed then die of

another illness still in the lead time

BMJ March 2006

The mammogram

� High standard� Good technique� Optimal positioning� Optical density� Processing� Labelling etc

Signs on a mammo

� Mass� Distortion� Asymmetric density� Small spiculate density� Micro-calcification

Benign lumps can look very malignant and malignant lumps can look very

benign

Beware!!

dimple

distortion

The assessment

� 1 in 8 recalled at least once in 10 y� Further mammography� Specialised views� Clinical examination� Ultrasound� biopsy

spiculate density

DCIS

� Ductal carcinoma in situ� Not an invasive tumour (yet)

Biopsy techniques

� Ultrasound guided (or freehand)� Stereotactic� Mammotome 8F or 11F

treatment

� Surgery� Radiotherapy� Neo adjuvant chemotherapy� Post op chemo� Hormonal manipulation� …….more later

Family history

� 13% clinic referrals (symptomatic)� Only 5% of all breast cancers have a FH

(also 5% <50y cancers have gene)

� BrCa1 and BrCa 2 genes (ov on BrCa1) gene carriers high % life time risk

� Others genes awaited

FH screening

� Pedigree assessed� Moderate or high risk offered screening� Annual 35y – 50y then…� Moderate into normal screening � High have 18monthly till 60y (Wales)

FH High risk

� > 4 relatives any age ( Br or Ov)� 3 relatives <40 y� If gene identified (only half have it)� 87% life time risk for Br Cancer� Prophylactic Mx� Life assurance etc

Moderate risk

� Br or Ov 1st / 2nd degree any age� Br 1st degree <40y� Male breast 1st degree� Bilateral breast 1st degree� Screening 1000 annually prevents 6 deaths

after 15y

� NB risk changes with time UP or DOWN

FH screening results

� Cohort Royal Marsden - 55 cancers� Annual screening BrCa 1 gene holders� Screen detected 56% � Palpation only 26%� Interval 11%� (DCIS 11%) ( grade lll commoner)

Powles 1997

Hodgkins screening

� Mantle irradiation for chest / neck nodes� Huge risk of breast cancer as a result� Breast vv radiosensitive < 19 yrs� Need screening – MR best, (mammo)

MRI

� Expensive� Limited availability� High sensitivity for ca breast� 77 % vs mam 40%� 94% if both MR and mam� Esp useful in BrCa 1 carriers

MRI

� 649 women (high risk ) annual sceen� 35 cancers occurred� 19 seen MR only� 6 seen mam only� 8 seen on both� (2 intervals)

Interval cancer

� Inevitable part of breast screening� Various types� True positive� False negative� Occult� unclassifiable

HRT

� Widespread use� Less now� Oetrogen + / - progesterone� Increase risks of breast cancer

HRT

� UK Million women study (UK) and Womens’ Health Initiative (USA)

� Risks higher on combined (RR=2.0) seen from 2 y

� 32 cancers non HRT group / 38 on combined (33.5 on Oest only) after 5years

� BUT 51 cases after 10 yearsCSM 2003

Treatment options

� Wide local excision or segmentectomy with radiotherapy post op

� Mastectomy +/- reconstruction (implant, lat dorsi flap, tram, Dieppe, etc)

� Chemotherapy neo-adjuvant or post surgical� hormonal

Wide local excision

� Palpable� Impalpable� Skin mark� Wire guided� Intra-operative x ray of excised specimen

Wire insertion – USS guided

Wire guided wide local excision

Mastectomy + / -

Rt mast / implant / nipple recon

Mast / implant /reconst nipple

Later… after tattoo

Reduction + mastectomy, implant etc

Sentinel node biopsy

SNB

� Single sentinel node removed� Reduces surgical morbidity� Reduces lymphoedema� Blue dye assisted - injected� Technetium labelled particles – injected� Do breast first � Then axilla

Indications for Chemotherapy

� Age� High grade (G3)� Nodal involvement� ER-ve� Vascular invasion� Size/ multifocaltiy� Co-morbidity

Risks/Benefits of Therapy

� The risks of any treatment must be balanced with the benefits for any individual

Benefits:� To prevent local recurrence of breast cancer� To prevent secondary disease� To effect a “cure”

Risks:� Physiological, mild to severe (death)� Psychological� Effect on QOL

HERCEPTIN

herceptin

� EXPENSIVE� £44,000 pa cf £73 for tamoxifen� Given IV� mg / kg basis� Oral preparation in the pipeline

THE TRIALS

� 4 MAJOR TRIALS (HERA in the UK)� Recruited 22,000 women

� Reduced the risk of first breast cancer event by 52% at 3 years

� Reduced the probability of a distant metastasis by 53% at 3 years

Herceptin

� Monoclonal antibody� Targets HER2 receptor (20% of breast

cancer)� HER receptors are a group of receptors that

regulate cell growth� When over-expressed in a breast cancer cell

causes uncontrolled growth� Herceptin targets the specific receptor and

switches of cell growth

Types of hormonal therapy

� Tamoxifen

� Aromatase inhibitors, anastrazole, letrozole, exemestane

� Ovarian ablation (surgery, RT, Zoladex),recent studies(ABC) no benefit

Side effects of hormone therapy

� Menstrual disturbance/affect on fertility� Weight gain� Hot flushes� Vaginal dryness� Loss of libido� GI upset� Endometrial cancer (tamoxifen)� Osteoporosis (AI’s)� Cardiac effects� Thromboembolytic episodes

Tamoxifen

� Tamoxifen is actually a very, very weak oestrogen, but it does not affect all oestrogen receptors in the same way

� Selectively INHIBITS oestrogen receptors on breast cells, stopping them from sending out the "grow and multiply" message

� Can STIMULATE oestrogen receptors in other organs � Tamoxifen may also very weakly inhibit the formation of new

blood vessels � Tamoxifen may even cause breast cancer cells to destroy

themselves, a process called apoptosis, or programmed cell death.

AROMATASE INHIBITORS

� STEROIDAL/IRREVERSIBLE; these include EXEMESTANE and irreversibly inactivates the enzyme

� NON-STEROIDAL/REVERSILBLE; these include ANASTROZOLE and LETROZOLE reversibly bind to the enzyme

� Compete with the enzyme aromatase that coverts androstenedione to oestrone and testosterone to oestradiol in the peripheral tissues

Bone protocol for AI use

� Significant increase in osteoporosis and fracture

� Fracture of femur carries significant mortality rate

� ? Need for screening e.g. DEXA scan� ? Need to omit those with a family history� ? Need for prophylactic bisphosphonates

NEW LICENCE INDICATIONS

� Anastrozole can be used in place of tamoxifen following diagnosis

� Exemestane can be used following 2-3 years of tamoxifen

� Letrozole can be prescribed following 5 years of tamoxifen for a further 5 years

thankyou