Hairmyres Hospital Breast Carcinoma Case Study Biology Essay

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Mrs. M is an 85-year-old lady who presented to AE of Hairmyres Hospital on 1/10/08 after being referred by her GP for a suspected advanced breast malignancy and a one week's history of low back pain with increasing severity.

She first noticed a lump on the lower outer quadrant of her right breast about a year ago. It was painless and measured approximately 2cm in diameter. She ignored the lump as it did not give her any troubles. Gradually, erythematous skin changes began to form surrounding the lump. With time, the lump progressively increased in size and was not mobile. She declined having any other lumps or local symptoms like skin itch and eczematous changes.

Later, she began to notice discharge from her right nipple which stained her shirt red. Despite all these presentations, she kept it away from her family and everyone else for fear that it might be cancerous. She admitted to self-medication where she had been applying mepore (to absorb leaking fluid from her nipple) and sudocream. Lately, she said that her right nipple had begun to leak foul smelling fluid which was dark in colour and the skin surrounding the lump turned greenish yellow. Recently, she decided to disclose her breast problems during a consultation with her GP for an increasingly aggravating lower back pain.

The new onset back pain was mainly localised to the lumbar region and was sharp in nature. Upon admission, she said the pain was quite severe scoring 8/10. There was no radiation, any associated muscle weakness or numbness. It was worse on getting up, straightening her back, walking and exertion like coughing. It was slightly eased by lying down. No injuries were noted. She declined having any urinary symptoms but was constipated the last few days prior to admission. She did not complain of any haematuria or PR bleed. She also did not notice any weight loss or change in appetite, rather felt that she had gained some weight possibly due to steroid inhalers for her COPD.

Past Medical History

Chronic obstructive pulmonary disease (COPD) - diagnosed 5 years ago.

Osteoporosis

Past fracture of lumbar spine (2004)

Family History

No significant family history.

Drug History

No known drug allergy.

Medication

Dosage/ Route

Frequency

Clexane

20mg, Subcutaneous

Once daily

Alendronate

70mg, Oral

Once weekly

Adcal Vit D3

1 Tab, Oral

Twice daily

Beclomethasone

250mg, Inhaled

Twice daily, 2 puffs each

Paracetamol

1g, Oral

4 times daily

Diclofenac

50mg, Oral

Thrice daily

Tramadol

100mg, Oral

4 times daily

Social History

Widowed 15 years ago. Husband died of prostate carcinoma.

Has 2 children who both live in Glasgow.

She lives alone in a double storey house and is finding it more difficult to climb the stairs lately due to her aggravating osteoporosis.

Came from a heavily smoking family and started smoking since she was about 20 years old. Smokes about 10-15 cigarettes a day.

Non-alcoholic.

Systemic Enquiry

Neurological

None to note.

Cardiovascular

None to note. No previous anginal pain.

Respiratory

Slight dyspnoea and wheeze.

Gastrointestinal

See above.

Genitourinary

None to note.

Haematological

None to note. No fevers or rigors

Musculoskeletal

See above.

Endocrine

None to note.

PHYSICAL EXAMINATION

General Inspection

Not distressed

Very mild pain on her lower back (controlled by analgesias given)

Appeared dyspnoeic (catched her breath from time to time during the interview)

Alert and non-lethargic

Apyrexial (Temperature - 37.1 0C)

Bruised over dorsal surface of both hands (due to repeated venepunctures)

Overweight (BMI - 28.5)

Breast Examination

Inspection

Asymmetry of breasts (Right breast more elevated)

Visible skin changes on the lower outer quadrant of her right breast

Green-yellowish lesion with central puckered skin

Surrounding erythema and satellite erythematous lesion

Spreading into axilla and upper border of right hypochondrium

No nipple retraction

Dark coloured fluid is seen discharging from the right nipple.

Palpation

Breasts

Axilla

Supraclavicular and infraclavicular nodes

Lump palpable on lower outer quadrant of right breast localised at site of skin changes. Diameter about 5cm.Hard, craggy, non-fluctuant and immobile.

No other lumps palpable and no lumps could be detected on left breast.

Right axillary nodes palpable most notably on medial aspect of right axillary wall.

None palpable on the left.

Palpable right supraclavicular nodes. Firm and immobile.

Musculoskeletal Examination

Examination of Mrs. M's lumbar spine elicited abnormalities.

Inspection

Kyphotic posture. Due to lumbar vertebrae fracture, gait is not tested in Mrs. M.

Palpation

Tenderness over L2-L3.

Movement

Decreased flexion and extension of lumbar spine

When hip flexed, pain increase in lumbar spine region.

No other neurological deficit elicited.

Respiratory Examination

Examination

Findings

Inspection

Hands

Mouth

Eyes

Chest wall

Slightly breathless

No peripheral cyanosis, warm hands

No finger clubbing/ no visible tar stains

No flapping tremor

No central cyanosis (tongue normal colour)

No jaundice

No anaemia

Slight kyphosis

Symmetrical movement of chest wall with respiration

No accessory muscles used in respiration

No visible scars

Trachea

Central, no tracheal tug

Palpation

Supraclavicular lymph nodes

Chest wall

Lymphadenopathy on right supraclavicular area

Normal expansion

Normal tactile vocal fremitus

Percussion

Resonant to percussion

Presence of cardiac and liver dullness

Auscultation

Scattered wheeze throughout both lungs

Coarse crackles, more notably on the lung bases.

Gastrointestinal Examination

Inspection

Skin

Hands and nails

Eyes

Mouth

Chest

Abdomen

Fragile skin (due to aging) with bruises from venepunctures.

No generalised skin pigmentation of haemosiderin

Not jaundiced and non-pallor

No palmar erythema / Non-pallor palmar creases / No dupuytren's contracture /

No asterixis

No finger clubbing, leuconychia, koilonychia

Non-jaundiced sclera

No Kayser-Fleischer rings (brownish green rings)

No xanthelasma or corneal arcus

Good oral hygiene

No glossitis or angular stomatitis or ulceration

No spider naevi

No scars but striae visible

No visible engorged veins or visible peristalsis or arterial pulsation

No caput medusae/ No Cullen's (blue discolouration of umbilicus)/ No Grey-Turner's sign (blue discolouration of flank)

Symmetrical movement of the abdomen with respiration

Palpation

Neck

Gentle palpation

Deep palpation

Liver

Spleen

Kidney

No enlarged supraclavicular lymph node

No tenderness or guarding

No abnormal masses or organomegaly

Soft, regular liver edge, not enlarged or tender, non-pulsatile

Not enlarged

Non-palpable

Percussion

Liver

Spleen

Shifting dullness

Normal liver span (<13 cm)

No dullness on complete expiration (no splenomegaly)

Absence of shifting dullness (no ascites)

Auscultation

Bowel sounds reduced

Cardiovascular Examination

Examination

Findings

BP

Pulse rate

135/ 80 mmHg

75 bpm

(regular, normal volume, no rebounding/collapsing pulse)

Inspection

Hands and nails

Face and tongue

Precordium

Back of chest

Ankle

Warm, absence of peripheral cyanosis

No finger clubbing/ splinter haemorrhages/ Osler's nodes/ Janeway's lesions.

No conjunctival pallor

No central arcus or xanthelasma

No central cyanosis

No visible scars or pulsations

Absence of sacral oedema

No pitting oedema

Jugular venous pressure

Not Raised (< 5 cm)

Palpation

No thrills or left parasternal heave

Auscultation

No murmurs heard

Crackles heard over lung bases

Neurological Examination

Nothing to note on motor and sensory examination.

MMSE: not carried out.

Cranial nerves intact.

Normal tone throughout upper and lower limbs.

Grade 5 power throughout upper and lower limbs.

Reflexes present throughout upper and lower limbs.

Normal coordination.

Summary of Problems

1. Advanced fungating breast cancer - Over the past one year, Mrs. M has hidden a fungating lesion on her right breast which was discharging blood stained fluid from her nipple and recently became foul-smelling. Due to lack of awareness compounded with fear, she now presents with an advanced breast malignancy.

2. Crush fracture of lumbar vertebrae - She presented with a new onset lower back pain with a duration of one week. Given a history of osteoporosis and past fracture of her lumbar spine, it is not known at present if the new fracture is due to an exacerbation of her vertebral osteoporosis or a metastastatic complication of breast carcinoma.

Differential Diagnosis

Differentials of clinical breast findings

a) Breast lump:

Breast carcinoma, metastasis to breast from other primary sites, intraductal papilloma

Benign breast disease (e.g. fibroadenomas, cysts, mastitis)

Breast lymphoma

Haematoma, thrombophlebitis, galactocoele

b) Breast skin thickening:

Inflammatory breast CA

Mastitis

In relation to Mrs. M's case, she presented with a right breast lump, surrounding skin changes (erythema and fungating greenish-yellow appearance) and foul-smelling, bloody discharge from her nipple which all point towards a high likelihood of breast carcinoma.

Differentials for Mrs. M's back pain in the lumbar region

Osteoporotic lumbar crush fracture

Metastatic bone disease from breast CA

Non-specific low back pain

Lumbar disc degeneration

Lumbar facet arthropathy, spondylolysis, spondylolisthesis

Psoriatic arthritis

Benign / malignant primary and neural osseous tumors

Extraspinal causes (eg, ovarian cyst, pancreatitis, ulcer)

Infection (eg, epidural abscesses, peritonitis) → unlikely as Mrs. M was not pyrexic or appeared to be in shock

Inflammatory conditions

Myeloma

Aortic aneurysm → likely in the elderly but Mrs. M does not have any pulsating abdominal mass

Aseptic necrosis of the femoral head

Renal infection or stone

Management Plan

Relevant Investigations and Results:

FBC

Hb

MCV

Platelets

WBC

14.1

88

189

9.6

CRP

38

U&E

Na+

K+

Cl -

Urea

Creatinine

133

4.9

99

9.2 (raised)

85

LFTs

Total Bilirubin

ALT

AST

Alk Phos

GGT

14

14

13

72

20

Serum amylase

85

Serum Ca2+

Adjusted

2.31

Coagulation

PT

PTT

Fibrinogen

10.2

26.6

4.6

Glucose

Fasting blood glucose

6.2

Lumbar Spine X-ray

Multiple crush fracture

(L2-L4)

ECG

Sinus rhythm

HR: 68

CT chest/ abdomen/ pelvis

Fungating lesion on right breast(Lower outer quadrant) -extending medially (41mm) and laterally (10mm).

One 12 mm chest and right axillary node.

Several tiny nodules on both lungs (Largest on right middle lobe 3-4 mm, the rests <2mm).

No mediastinal lymphadenopathy.

Abdomen and pelvis grossly normal.

Probable osteoporotic collapse (L2-L4)

Core Biopsy of right fungating breast CA (Clinically P5)

Oestrogen and progesterone receptors - >90% of tumour cell nuclei strongly +ve

Allred score 5+3 = 8

Invasive CA (poorly differentiated ductal CA)

No in-situ CA

No vascular invasion

Core biopsy B5b

Initial Treatment of Acute Problems:

Provide adequate analgesia

Perform routine bloods, ECG, CXR and lumbar spine X-ray (to determine if there is lumbar fracture)

Myeloma screen

Perform CT scan of chest, abdomen and pelvis

Perform core biopsy of right breast lesion

Perform bone scan to determine if there are focal hot spots indicating bony mets from primary breast CA

Further Management Option:

Physiotherapy / Occupational Therapy assessment

Give low molecular weight heparin to prevent DVT from restricted mobility due to lumbar spine fracture

Conservative management of lumbar spine fracture (pain relief, bracing and rehabilitation). Consider thoraco-abdominal-sacral orthosis. Early mobilization is important to prevent secondary complications of immobility.

Core biopsy confirmed invasive ductal carcinoma - Discuss management options with patient. Address to Mrs. M' s fears of a cancer diagnosis.

Reflective Commentary

Breast cancer is the commonest cancer in women. [1]

Breast lumps can be classified into:

Aberrations of normal development and involution

Benign neoplasms - e.g. fibroadenoma (most common).

Malignant neoplasms -non-invasive and invasive malignant tumours.

Prognostic Factors [3]

Following surgery, a number of prognostic factors determines outcome and plan adjuvant therapy.

Type of tumour

Tumour size

Tumour grade - well differentiated (Grade I) do better than poorly differentiated (Grade III)

Axillary lymph node status - 1 node +ve (80% survival at 5 years); 4 nodes +ve (50% survival at 5 years)

Presence or absence of lymphovascular invasion

Hormone receptor status - ER+ve have better prognosis and responds to tamoxifen.

Factors 2-4 combine to form the Nottingham Prognostic Index (NPI): [3]

NPI = 0.2 x size (cm) + grade + nodal status

NPI Score 10 Year Survival

<2.4 95%

2.41 - 5.4 50% to 85%

>5.4 20%

Pathology [2]

Pathologically, breast carcinomas are divided into 2 main types:

Non-invasive / Carcinoma in-situ

Malignant cells remain within basement membrane.

Ductal carcinoma in situ (DCIS)

Lobular carcinoma in situ (LCIS)

Paget's disease of nipple

2) Invasive

Malignant cells extend beyond basement membrane.

Invasive ductal carcinoma

Invasive lobular carcinoma

Special types

Tubular

Medullary

Mucinous / colloid

Clinical Presentation

Classical presentation may include the following where breast asymmetry is the commonest.

Adapted from Ref [3]

Signs and symptoms

Elaboration

Lump

Nodular, irregular, immobile and non-fluctuant with menstrual cycle are normally malignant.

Skin changes

Skin tethering or dimpling due to fixation to overlying skin or underlying pectoral muscle.

Peau d' orange - swollen, pitted skin overlying breast CA due to lymphatic obstruction.

Nipple eczema - Paget's

Surface ulceration

Nipple discharge

Blood-stained

Nipple retraction

Due to contraction of intramammary ligament (Cooper's)

Non-cyclical breast pain

Late stage presentation.

Metastatic complaints

Bone - pathological fractures

Liver- jaundice, hepatosplenomegaly

Lungs - dyspnoea, pleural effusion

Comparison of the Patient's Presentation to Classical Presentation:

Mrs. M presented with a hard, immobile lump on the lower outer quadrant of her right breast (measuring about 5 cm now). There are visible skin changes surrounding the lump which are typical of advanced breast cancer i.e. erythema and fungating greenish-yellow appearance. She also complained of bloody nipple discharge which is purulent and foul-smelling indicating that the intraductal lesion is undergoing inflammatory changes. In summary, Mrs.M's presentation is classical of advanced fungating breast carcinoma. It is little wonder that she does not experience any breast pain as only 2.7% of patients with mastalgia have cancer. (1)

How this case relates to the GMC themes in 'Tomorrow's Doctors':

Theme 2: Treatment & Theme 11: The Individual In Society

Investigations

The diagnosis of discrete breast lumps is based on triple assessment:

1) Clinical examination - palpation

2) Radiological imaging

Mammography in older patients (above age 35).

Ultrasound in younger patients (below age 35) due to dense breast tissues.

MRI useful in symptomatic patients with breast implants.

3) Biopsy, usually ultrasound guided

Fine needle aspiration cytology (FNAC)

Core biopsy - provides histological diagnosis and distinguished between invasive and in-situ carcinoma.

Breast

Triple assessment

Repeat core biopsy

Discharge

Open biopsy

Benign (definite lesion)

Reassure unless radial scar

Suspicious or atypical

Repeat core or open biopsy

Definitive treatment

Benign

Concern whether sample is adequate

Lesions adequately sampled

Malignant

Investigation of a breast mass : Adapted from Ref (1)

Management

The principles of management are:

Establish diagnosis

Control disease in affected areas

Prevent and treat local disease in early breast CA

Control metastatic disease

Surgery

a) Breast conserving surgery - involves lumpectomy (WLE), quadrantectomy, or segmental mastectomy with or without axillary dissection and adjuvant radiation therapy.

Fisher et al found that this is as effective as mastectomy for small operable breast cancer.[7]

b) Radical (Halsted) mastectomy

Removal of entire breast used to be the preferred in the past combined with axillary clearance +/- breast reconstruction.

c) Surgery to axilla

Axillary node status is most important prognostic indicator in treatment of invasive breast CA.

Axillary sampling - involves removal of a minimum of 4 nodes for histology. If any of the 4 nodes are +ve, further treatment either axillary clearance or radiotherapy is required.

Axillary clearance - currently, level II dissection is performed where nodes up to axillary vein and beneath pec minor are removed. This results in more breast lymphoedema.

Sentinel lymph node biopsy (SNLB) - first lymph node draining the cancer field is identified, excised and examined for metastatic involvement. This prevents extensive axillary surgery if no node involvement found.

d) Breast reconstruction

Either done during mastectomy or delayed to a later date.Typical reconstructions use latissimus dorsi or rectus abdominis, augmented where necessary with silicone implant.

Adjuvant Systemic Therapy

Reduces risk of relapse by 30-40%. [1] The choice of therapy depends on NPI.

a) Adjuvant chemotherapy - currently used for most pre-menopausal with high-grade tumours, axillary spread and hormone receptor -ve, but without evident distant mets. [8]

Most widely used regimen is CMF (cyclophosphamide, methotrexate, 5-fluorouracil).

The effect of chemotherapy on advanced fungating breast tumours has been widely studied, and generally, it has been found to be effective for reducing the tumour size and healing the fungating wound. [8]

b) Adjuvant hormonal therapy

Tamoxifen (oestrogen receptor blocker) reduces recurrence by 25%/ year and mortality by 17%. Tamoxifen is most helpful in node +ve and ER+ve women and is recommended for 5 years.

In post-menopausal women, aromatase inhibitors (anastrozole, letrozole and exemestane) and progestogens (megestrol) can be used.

c) Immunotherapy

Humanised monoclonal antibody trastuzumab, raised against HER-2, increases rate and duration of response of patients with metastatic disease (HER-2 +ve) when combined with chemo.

d) Adjuvant radiotherapy

Following WLE, radiotherapy significantly reduced recurrence within the breast. Recent studies shown that pre-menopausal women receiving adjuvant chemotherapy, post-mastectomy radiotherapy may also improve survival. [1]

In metastatic or advanced breast cancer, primary aim is palliation either by hormonal or chemotherapy.

Mrs. M presents with an advanced fungating invasive ductal carcinoma which further reduces her treatment options. However, she should still be allowed to make active decisions about her treatment. With an ER+ve tumour from core biopsy, she may be a candidate for hormone therapy. The best adjuvant treatment option for her can be more accurately determined by NPI which is only possible post-operatively. Given her advance age and pre-existing COPD, surgery is a definite contraindication. Therefore, it is most important that Mrs. M is provided with adequate information about all the available options for her case and her decision given the utmost respect.

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