Breast Cancer

1) HistoryMrs DG• 54 Years old, married, teacher• No current medical illness• Post meneopausal since 49 years old• Two daughter aged 29 and 26• Mrs DG Hormone Replacement Therapy btwn ages of 51 and 53• Used OCP btwn ages 40 and 45• Drinks standard drinks of wine daily• Maternal aunt – diagnosed w breast cancer at 71• First live birth – 25• Onset of menarche was 13 years old• Weight 82kg + 168cm tall• Never had benign breast disease, has had normal screening mammograms at age 51 and 53

2) Risks of developing breast ca :1) Age – increase in agE2) Lifestyle – obesity and alcohol intake3) Biopsies – women who have had breast biopsies, increased risk of breast cancer, esp if it showed atypical hyperplasia. 4)Family Hx – first degree relatives w Hx of bilateral breast ca or Dx at young age 5) Parity – younger age at first live birth = higher risk, #of affected relatives more = higher risk6)menarche age – women w first menstrual period before age 12 increased risk of breast cancer, linked to longer lifetime exposure to oestrogen

3) Breast cancer review Btwn 2nd and 6th ribs, from sternal edge of axilla and against pectoralis

muscle on chest wall Divide 4 quadrants; upper inner,upper outer,lower inner, lower outer Most often – upper outer quadrant 15-20 lobes, each lobe surrounded by fat + fibrous connective tissue n

divide into many lobules each lobules subdivided into 10 to 100 alveoli, milk producing unit of

breast. Lobulesductsnipple Main ca – ductal carcinoma(85%) lobular carcinoma (15%) Lymphatic vessel – axillary LN

Breast development aka mammary fold or milk line age 10/11 – relase of oestrogen and progesterone – futher development

of breast tissue adulthood – complete, menopause – lobules recede, leaving mostly ducts,

adipose and fibrous tissue. Postmenopausal+ prepubertal similar menstruation – rise oestrogen n progesterone – ducts and milk glands

enlarge

pregnancy – lobules dilated and engorge w colostrum and milk lactation – increase risk of abnormal nipple discharge, infection and

inflammation

Breast changes Divided 2 :

a) Inflammatory – infectious, trauma etcb) Benign epithelial lesion – fibrocystic changes (hormonal&genetics )

Fibrocystic changes type :

a) Nonprolifeative changes Histological : cysts, nonsclerosing adenosis, ductal ectasia, lactational

adenoma, simple fibroadenoma, mild hyperplasia

b) Proliferative changes without atypia Excessive cell growth, esp duct linings Intraductal papilloma, radial scar, sclerosing adenosis, complex

fibroadenoma, moderate or florid hyperplasia Elevated risk of developing breast ca

c) Proliferative changes with atypia Excessive cell growth w cell appearing abnormal Atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH)

may be difficult to diff from ca – either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS)

Atypical – 4 to 5 times increase RR for breast ca

Type of breast Ca Inc in no of breast cells (hyperplasia) to emergence of atypical breast

cells(atypical hyperplasia) followed by carcinoma in situ(noninvasive cancer) and finally invasive cancer

Noninvasive Breast Cancer

A) Ductal carcinoma in situ (DCIS) – most common Uncontrolled growth of cells that confined to breast duct Any cellular changes beyond atypical hyperplasia Very few cases of DCIS present w palpable mass; most diagnosed by

mammography – clustered microcalcifications Pathological nipple discharge w/w.out mass Early detection – 5yr survival – provided ca doesn’t spread to milk

ducts

B) Lobular carcinoma in situ (LCIS) – less common Abnormal changes of lobules, multiple lesion + bilateral Less risk invasive compared to DCIS AKA lobular intraepithelial neoplasia Incidental findings tru biopsies, not mmography

Invasive Breast Cancer

A) Invasive (infiltrating) ductal carcinoma [IDC]– most common AKA infiltrating ductal carcinoma Cancer cell penetrated ductal wall n invaded breast tissue,metastases Hard + firm palpable mass,mammographic abnormality Skin + nipple retraction

B) Invasive (infiltrating) lobular carcinoma [ILC] – uncommon At lobules to adipose tissue of the breast Palpable mass w less well-defined, difficult to detect by mammogram

C) Tubular carcinoma Highly differentiated, regular and arranged in well defined tubules cell Incidental findings, nonpalpable mammographic abnormalities

D) Medullary carcinoma – uncommon Wel-defined boundries, large and soft on plapation

E) Mucinous carcinoma AKA colloid carcinoma Large amout of extracellular mucin production In postmenopausal women, not palpable tumor Well-circumscribed and microlobulated margins

F) Metaplastic carcinoma - uncommon Palpable lesion ass w rapid growth Mammographically, fairly circumscribed, noncalcified lesion, benign

G) Invasive cribriform carcinoma – small n unifrom cellH) Invasive papillary carcinoma – rare, postmenopausal,nodular densitiesI) Invasive micropapillary carcinoma – firm, immobile mass, rare

OthersJ) Inflammatory breast cancer - rare Sx : breast inflammation, warmth, thickening or dimpling (peau d’ orange)

palpable ridge margin of induration Results from blocking of lymphatic vessels near surface of skin by cancer

cells

K) Paget’s disease of the nipple Sx : erythema, mild scaling of the nipple skin, more advanced if nipple

tingling, itching, increased sensitivity, burning, pain or oozing

L) Phylloides tumors Benign/malignant – rare Benign epithelial elements and cellular connective tissue stroma Painless4) Clinical feature of breast lump suggest malignancy?

Hardness

Irregularity Focal nodularity Asymmetry with the other breast Fixation to skin or muscle Skin changes like peau d’orange

Continue Hx : Mrs DG had lump in upper outer quadrant of the breast. No bleeding or discharge from nipple. No pain or heaviness. No nipple inversion or Peau d’orange skin changes or skin ulceration. No palpable LN, PE normal.

5) The triple test Medical Hx and clinical breast examination Imaging w mammogram (MMG) and/or US Non-excision-fine needle aspiration (FNA) cytology and/or core biopsy

-must follow order-the triple test is positive if any component is indeterminate, suspicius or malignant-US more sensitive in detecting ca in younger pt- US first modalities for <35y/o patient + pregnancy or lactation-Mammography first modalities for >50y/o-Mammohraphy or US for pt btwn 35 and 50 y/o-Core biopsy + FNA are complementary-Core biopsy show invasive disease wherease FNA cant diff btwn in situ and invasive cancer

Continue Hx : Mrs DG told by GP, breast biopsy confirm maligancy referred to breast surgeon. Confirm early breast ca + operable w no c/I to surgical removal.Primary surgical Mx addressess 3 issues :• Local Control of the Disease within the Breast• Local Control of potential lymph node involvement in axilla• Provide histology for pathologist to advise on prognosis for local

and systemic recurrence.-advised breast conservation w sentinal LN + radiation depend on result patho

6) Reason for mastectomy Patient choice Contra-indication to receiving radiation A large tumor relative to size of breast Positive surgical margins despite re-excision and likely poor cosmtic

outcome w further re-excisions Multi-centric cancers in diff quadrants of breastContinue Hx : Mrs DG undergo surgery

7) Routine assessment for fitness before surgery :

Blood tests : FBC,Coag, U&E, LFT ECG CXR Bone scan, CT Chest adbomen and pelvis – stage T3/T4 or multiple

clinical palpable axillary nodes Brain CT – morning headaches w vomitting, neurological deficit

suggest intracerebral metastases

8) Histological characteristic of breast cancer that predict local or systemic recurrence?

T – Tumor siza N – LN involvement M –Distant metastases

Prognosis and therapeutic decisions are made according to the TNM, estrogen-receptor (ER) and progesterone-receptor (PR) levels in the tumour tissue, as well as:

•    Human epidermal growth factor receptor 2 (HER2/neu) status in the tumour tissue •    menopausal status •    general health of the patient.

9) Breast cancer progression and staging

Stage 0 – non invasive, not spread beyond breast tissue

Stage 1 - < 2cm, no spread beyond the breast

Stage 2(a) – invasive, </= 2cm + spread LN under arm OR 2-5cm and has not spread to LNStage 2(b) – 2-5cm spread to under arm LN OR >5cm not spread to LN

Stage 3(a) - <5cm + spread under arm LN fuse each other forming clump OR spread LN near breast // >5cm under arm LN x clumpingStage 3(b) – any size, spread to chest wall and skin and swelling breastStage 3(c) - any size, spread to chest wall skin

Stage 4 – metastases + spread to other organ

Continue Hx : histology reveals19mm Grade 3 invasive ductal carcinoma, no lymphovascular invasion, margins are clear, some in-situ disease (EIC negative). 1 of 2 sentinel nodes weak +ve, PR –ve, Her 2 –ve(IHC stain chromosome in situ fluorescence –ve)

Normal breast with DCIS in an enlarged cross section of the duct

 R - Range of ductal carcinoma in situ (DCIS)L – Invasive ductal carcinoma with ductal cancer cell breaking trough basement membrane

Key:A: ductsB: lobulesC: dilated section of duct to hold milkD: nippleE: fatF: pectoralis major muscleG: chest wall/rib cage

10) Mrs DG Pathology result and treatment plan – script

Hello Mrs DG ( and family) , please take a seat.( pause to allow to sit down and shut the door). I would like to discuss with you the results from your second operation. You will be pleased to hear that the rest of your lymph nodes were clear of cancer cells-which is good news. (pause to allow patient time for this to filter in). However, because one of the 17 lymph nodes in total contained cancer cells I would like you to see a medical oncologist to discuss any other treatments that may improve your chance of being cured. You will also need to see a radiation oncologist as you will need to have radiation treatment to the remainder of your breast. You’ll remember we discussed this when I first met you that when we remove only the breast lump to  conserve your breast, radiation is needed. I would like to go over the rest of your pathology again so you understand the treatments the medical oncologist may recommend......(pause) We know the tumour was middle of the range in size at 19 mm– it was not small (which we call less than 10 mm) but it was not large either. But from the grade-that is how aggressive it looks under the microscope-we know it is more aggressive being a grade 3 where 1 is low grade, 2 is middle of the range and 3 is aggressive. ( pause)..... The good features however  in terms of your risk of the cancer coming back are that there was no evidence of invasion into the blood vessels or lymph vessels, that another protein called the Her 2 protein was absent  in the tumour tissue   and that is shows some sensitivity to hormones by staining positive for the oestrogen hormone. When you see the Medical oncologist they will discuss with you the options of chemotherapy and hormone blocking therapy....  ( pause). I think it is likely they will recommend both as you are young and previously fit. (if expansion on this required  .......Chemotherapy is given all as an out-patient treatment, takes a couple of hours and usually given once every 3 weeks on six occasions. It will be supervised by the doctor. You will not vomit as the medicines to treat nausea are much better these days but you will lose your hair. ( pause and ascertain if this is a problem). It will grow back after all the treatment is finished and the cancer centre provides a wig and scarf service. It is likely you will feel tired whilst on the chemotherapy which again improves after the chemotherapy finishes after a few months. Other changes you may notice are sometimes a sore mouth so you will need to do mouth washes after meals. Sometimes too there is diarrhoea. Chemotherapy can affect your immune system and if you have a fever or a temperature any time in those 18 weeks you will need to go to hospital in case you need special antibiotics. The doctor will also check your heart function before you start given your blood pressure problems and being a smoker as some of the chemotherapy treatments can affect the heart

muscle and the treatment may change if there are problems. Remember...these are possible side effects but they may not happen and the doctor will make any changes each treatment if there are any problems.( if expansion on this was required) You might ask how this will affect you working and your home life. Some people feel well enough to continue whilst some stop during their treatment. I would discuss this with your work to warn them of this- most employees are understanding. I can sign another work certificate for you today covering you until you’ve seen the oncologists. The Radiation is given after chemotherapy is completed and usually takes up to 5 weeks with each treatment given daily Monday to Friday taking a few minutes each day ( about half an hour by the time you’re parked and then booked in and lined up). It’s a bit like having an xray people say. Before the treatment starts the radiation doctor will need to place some tiny markings with a tattoe the size of a small dot to make lining up each treatment easier. The radiation can also make you feel tired and sometimes the breast skin develops a redness like sunburn which can occasionally worsen and peel, but they will keep an eye on you and help you and it will improve within a couple of weeks generally. At the end of radiation the Medical Oncologist will talk to you again more about the hormone blocking treatments. We sometimes call it endocrine treatment. This is in the form of a tablet and is taken daily for usually 5 years. Some of the side effects include hot flushes, others depend on which tablet you are prescribed and may include mild joint aches and risk of thinning of the bones, others a slight increased risk of blood clots in the legs or lungs or changes in the lining of the womb. Pause....this is  alot of information for you today I know... Let me give you with a guide to breast cancer treatments provided by the called “My journey” kit, provided by the Breast Cancer Network of Australia to help you. Let me help fill in the section about the stage of the cancer and what the pathology showed to help you when you go home. This must be a difficult time for you with lots of uncertainties but with more information about the treatments available I hope this will help allay any fears you have. Our breast care nurse ( who I think you met in hospital)  is available to discuss anything before and after meeting the oncology doctors and sometimes they may refer you to their cancer social worker and cancer psychologist  to help you talk to your work as well as your 2 children. ( pause) I’ll just write the contact number of the breast care nurse for you in your book.... Is there anything you would like to ask or clarify at this time? ( pause) Have a think while I am checking your wound but feel free to give me a ring to talk some more over the phone if you need to. 

Well that’s all looking well healed. So just to summarise... the cancer has all been removed and we found only one gland in your axilla contained tumour.  I would like you to discuss both chemotherapy and hormonal blocking therapies as a further way to improve your chances of being cured, as well as seeing the radiotherapist. I’ll contact your GP about what we have discussed today in case you wish to discuss things further with him/ her also. Do you have any questions? (pause) ..... I would like to see you in the next couple of weeks by which time you may have seen the medical and radiation oncologists. We’ll be discussing your case again at the meeting with them I mentioned before once they’ve met you so they’ll also update me. I’d also like to see you a couple months after you finish your chemotherapy and radiation treatments whatever you decide. 11) Difference between chemotherapy and radiation therapy?

Chemotherapy Administration of drugs intravenously although sometimes can be given

orally As chemotherapy enters the bloodstream the drugs are delivered

throughout the whole of the body Kill all rapidly dividing cells

Radiation therapy X-ray beams generated from a machine called linear accelerator and

directed to a specific are Tx modalities is different therefore hv diff side-effect profile

12) Intention of radiation therapy? Cancer Mx involves multiple modalities of Tx, combined surgery,

chemotherapy, and radiation therapy. Support main treatment and improve cure rate Breast ca – definitive Tx is surgery. But certain like early laryngeal ca,

radiotherapy may be definitive Neo-adjuvant – b4 definitive Tx, reduce size of, or to down stage, the

primary tumour., do chemo or radiotherapy, treat residual misroscopic disease

Adjuvant – additional therapy after definitive therapy Radiotherapy – Mx of early breast ca should be consider as adjuvant Palliative Tx – for pt whose disease is not curable

13) What should be included in radiation therapy? In early breast ca, radiation therapy is integral part of local Mx Radiotherapy following local excision – improve local control

14) Side effects during a course of radiation therapy?

Oedema Fatigue Skin reaction (sunburn effect)

+ Delivery of radiotherapy – painless procedure+ Only systemic SE – Fatigue+ Pt only experience hair loss if hair is within radiation field.+SE like nausea, vomiting or mouth ulcers – associated w chemotherapy+Radiotherapy – associated with delayed or late effects related to a fibroblastic reaction causing fibrosis and scarring; depends on total dose of radiotherapy of the organ being irradiated.+Acute SE – fatigue,oedema of her breast, skin reaction+Late SE – fibrosis, breast pain or tenderness, scarring of the lung adjacent to the chest wall immediately under the breast+ Secondary malignancies w radiotherapy – RARE!

As follow-up, Mrs DG should have yearly MMG.

Should have follow up with surgeon, medical oncologist, radiation oncologist, and performed breast examination herself.

Every 3 months in first yr and every 4 months in second year then in yr 4 and 5 every 6-12 months

MMG and US must be performed Must also stop smoking

Post-treatment surveillancePost-Tx MMG MMG one yr after your 1st MMG that led to Dx,but no

earlier than 6mnths after radiation therapy. Obtain MMG 6-12mnths thereafter

Breast self exam Perform every month.Pelvic exam Continue visit gyn regularly. Women taking tamoxifen

should report any vaginal bleeding to their doctorCoordination of care Continue visit onco or GP. Women taking hormone

therapy should get dr to re-evaluateTell your doc if you experience :

1) new lumps in the breast2) bone pain3) chest pain4) abdo pain5) SOB6) Persistent headaches7) Persistent coughing8) Rash on breast9) Nipple discharge

15) Key factors that increased risk? Multiple relatives affected by breast cancer (male or female) or ovarian ca Younger age at cancer Dx in relatives Relatives affected by both breast and ovarian ca Relatives affected with bilateral breast ca

Ashkenazi Jewish ancestry

16) Accurate family Hx? Asking woman about any primary cancer in all 1st degree (parents,

siblings,children) and 2nd degree (aunts,uncles,nieces,nephews,grandparents) relatives on both sides of the family.

Establish site n age at Dx of ca Confirm, if possible, reports of ca in relatives Update family Hx regularly