Breast Carcinoma Breast Carcinoma Breast Carcinoma Breast Carcinoma Detailed History of Presenting Illness (HPI) - small, firm, irregular lump in the breast- with/without dimpling or oedema (“orange skin” appearance) - nipple retraction/discahrge

List of Differential Diagnoses (DDx) - Cancer (9 out of 10 presenting lumps are not cancerous) - Fibrocystic change (Adenosis, an increase in the number of acini within lobules, occurs as part of fibrocystic change) - Apocrine metaplasia (may develop in adenosis) - Microglandular adenosis (a benign gland-like proliferation but not resembling lobules.) - Radial scar (mammographically indistinguishable from carcinoma: frequently calcified and have irregular stellate shapes) - Benign Papillary Neoplasms - Breast Abscess, lactational (3wks post-partum) or non-lactational (mainly women 18-50y.o.; 90% are smokers) - Breast Cyst (common in the 5 years before the menopause) - Ductal hyperplasia (not malignant but indicates a risk of malignancy)

- Fibroadenoma ( a benign neoplasm, which arises from the epithelium and stroma) - Trauma i.e. haematoma, or bruise

List Pertinent Findings on History (Hx) - Lump has existed for HOW LONG? - How large? Enlarging? Cycling (waxes/wanes, regular/intermittent)?

- Age at menstruation - Age at menarche - Previous pregnancies - Breastfeeding-Y/N - Oral contraceptive use - Hormone Replacement Therapy (any medications at all?) - Last mammogram - Frequency of self-examination –SHOULD BE MONTHLY !! - Previous malignancy - Family history of breast cancer List pertinent findings on Examination (Ex) Nil relevant for body systems BREAST LUMP: how to examine: @ DAY 5-7 of MENSTRUAL CYCLE

Visually inspect 1st : arms at the sides; Advise Pt as you proceed (educating them for self breast examination)

if notice abnormalities, etc – be discrete and inform Pt later. -obvious deformity? attention to

- size, - shape or position, - dimpling or puckering of the skin, - pushed-in or misshapen nipples, - other changes in the nipple - redness, swelling, pain / tenderness- CARDINAL SIGNS OF INFLAMMATION?

Then, repeat this process with the Pt placing hands on the hips, pressing firmly to flex the pectorals.

Palpate in seated: begin by sliding hands along top of clavicle (feeling for supraclavicular nodes)

– Work superficial ⇒ deeper. CHECK FOR NODES IN AXILLA: POST + ANT AXILLARY WALL

– Use the pads of the fingers, not the tips – Check nipple for discharge; push in to check for underlying mass

– Use following chart of palpating directions

breast exam should then be repeated with Pt lying supine –allows compression of breast tissue against chest wall and distributes breast tissue. One arm up over head in sunbaking position.

Don’t forget to include axillary tail.

SUSPICION= fixed, hard, irregular painless lump.

NOT SUSPICIOUS? Come back for follow up; re-examine.

put together by Alex Yartsev: Sorry if i used your imagesor data and forgot to reference you. Tell me who you are.

aleksei.igorevich@gmail.com

How is this diagnosis made ? (most breast cancer is diagnosed by BIOPSY) FLOWCHART OF DECISION-MAKING MECHANISM: …RISK FACTORS PLAY NO PART! Definition Of MASS: – in PRE-MENOPAUSAL WOMEN: lasting through the menstrual cycle – in POST-MENOIPAUSAL WOMEN: any detected mass

NO yes MAMMOGRAM

Screening is (should be) promoted for women over 40: ~85% will survive if caught early

-looking for calcification (radiating spicules infiltrating into the surrounding tissues), atypical enlargement,

density. Optimum effect = having previous mammograms to compare; ALWAYS compare to healthy breast (Rt)

MASS Suspicious? Not Suspicious?

MAMMOGRAM

MAMMOGRAM

ULTRASOUND

Characteristic stellate solid mass?

FINE NEEDLE ASPIRATION: Histopathology

OBSERVATION

EXCISIONAL BIOPSY: target histopathology for management options

Benign? Malignant?

ULTRASOUND -used to differentiated fluid cysts from solid masses; -a palpable mass that is not visualised on ultrasound must be solid. Characteristic Appearance:

Irregular hypoechoic (dark) mass with posterior shadowing (no ultrasound echoes). Can be used to guide FNA biopsy

FINE NEEDLE ASPIRATION BIOPSY Unskilled hands = false negatives (completely miss the tumour); + there is some chance of spreading the cancer if malignant and invasive VERY RARELY will all 3 methods give false negs (i.e palpation � mammogram �FNA); chance = 1% MUST CHECK ESTROGEN RECEPTORS: v. important, ER +vity qualifies for Tamoxifen tmt

EXCISIONAL BIOPSY – Amounts to treatment for small lesions; results (margins, histology) dictate further management – Most accurate and reliable method

Disease Definition Multistage genetic transformation of breast ductal or lobule cells into poorly regulated growth resulting in

proliferation and spread of cancer.

Management Best Treatment Ever: Radical Mastectomy (for all pre-metastatic cancers regardless of size) Removal of the breast tissue (this alone constitutes a “modified radical mastectomy”) Removal of the underlying deep fascia and pectoralis muscle Removal of lymph nodes from the region.

- Combined local + distant recurrence rate = 1 to 2% for 5 yrs A patient's age should not be a determining factor in the selection of breast-conserving treatment versus mastectomy.

SUBTYPE-SPECIFIC TREATMENTS FOR EARLY BREAST CANCER Ductal Carcinoma In Situ , Medullary Carcinoma -and all non-invasive localised cancers; -excellent prognosis ~100% survival in patients with small lesions (</=1cm) after lumpectomy + radiation)

1) Lumpectomy (breast-conserving surgery) - the removal of gross tumour and generous margin of tissue:

local relapse rate of margins >5mm was 0% after 12yrs

2)Chemotherapy Patients treated with lumpectomy and radiation will also be candidates for chemotherapy- BUT ONLY if they have - lymph node metastases (rare with DCIS and most other localised small cancers) - high risk tumors (inflammatory carcinoma, tumours 2cm or larger, unfavorable DNA studies, hormone receptor negative cancers) even if nodes are negative.

if the odds of a cure are already very high,

the benefits from chemotherapy may be quite small while small tumours are more susceptible to chemotherapy than larger tumours,

..they also regrow at a faster rate most therapists give the chemotherapy first and the full course of radiation after

3) Radiotherapy of: – -the breast to 45-50 Gy – -the affected lymphatics to 45-50Gy- yes, DCIS can have lymphatic spread, so biopsy those nodes! – the immediate tumour bed to an additional 10-16 Gy (reduces local recurrence: most recurrence is in scar)

– RADIOTHERAPY + SURGERY is JUST AS GOOD AS RADICAL MASTECTOMY in controlling recurrence

MANAGEMENT OF INVASIVE LOCALISED CANCERS Invasive Ductal Carcinoma, Invasive Lobular Carcinoma, Infiltrating Ductal Carcinoma, etc.

1) Surgery: not much difference between

LUMPECTOMY + axillary nodal dissection

Vs. MASTECTOMY (modified radical; ) 5yr local recurrence rates were 2.8% and 4.3% respectively

2) Chemotherapy: – adjuvant chemotherapy reduced the relapse rate by 23.5% and the mortality rate by 15.3%. (drug combination CMF(cytoxan, methotreaxate, fluorouracil)) 3) Radiotherapy:

-Post-Lumpectomy treatment is IDENTICAL to the regime used for non-invasive cancers

If necessary the irradiation extends to the lymphatics of the axilla and the supraclavicular region

increases the survival rate by 5 - 10%.

PostMastectomy Radiation Therapy:

will decrease local relapses by 2/3;

Most useful for pts with 4+ positive nodes

MANAGEMENT OF ADVANCED STAGE BREAST CANCER Treatment for systemic disease is palliative in intent.

Goals of treatment include improving quality-of-life and prolongation of life. Surgery may not be an option if cancer has spread to bones, liver, etc.

Palliative Radiation: 30 Gy in 10#, 20Gy in 5#, 8Gy in 1# - APPLIED TO AFFECTED SITE Currently, the rates of survival with bone metastasis and radiation are 73 weeks for a solitary lesion and 34 to 48 weeks with multiple lesions.

TAMOXIFEN is also a means of relief for metastatic ER +ve breast cancer patients with widespread

systemic disease

Prognosis Excellent if treated early and the tumour is small; declines depending on treatment and overall health

Epidemiology – PEOPLE WHO PRESENT WITH LUMPS:

– 30% have no disease – 40% have fibrocystic change – 13% misc benign – 7% fibroadenoma – 10% have cancer:

– IN SITU = 15 - 30% – INVASIVE = 85 - 70% – Ductal 79%, lobular ~10%, everything else = 11%

– most commonly upper outer quadrant (50%), slightly more commonly left breast (11:10) –

Aetiology / risk factors: – SINGLE BIGGEST RISK FACTOR IS AGE – Breast cancer in family – Obesity – Previous breast cancer or endometrium cancer – Age of 1

st prenancy more then 30 yrs

– Long reproductive life – Alcohol and Smoking

RISK GROUPS: I: At or slightly above average risk Lifetime risk: Between 1 in 13 and 1 in 8

– no family history – a first or second degree relative diagnosed with breast cancer after the age of 50. – comprises about 95% of all women. – At most, these women have a risk increased by 50% over the general population.

II: Moderately increased risk Lifetime risk: Between 1 in 8 and 1 in 4 – One or more first or second degree relatives on the same side of the family with breast cancer, before the age of

50 years. – comprises less than 4% of all women.

III: Potentially high risk Lifetime risk: Between 1 in 4 and 1 in 2

– (or higher if known to have inherited a breast cancer gene mutation. )

– have breast or ovarian cancer (including breast cancer in males) diagnosed in three or more first or second degree relatives on the same side of the family,

– members of recognized high-risk cancer syndromes, such as Li-Fraumeni or Hereditary Non-Polyposis Colorectal Cancer. comprises less than 1% of all women.

Pathophysiology / Pathology Cell biology: the cell cycle

WELL BEHAVED CELLS: – need specific signals to undergo mitosis – quiescent while there is no signal – Require Survival factors while quiescent: else, Apoptosis – Require Anchorage

Cell cycle Checkpoints are protected from instability: failed checkpoint = cell cycle arrest and apoptosis Positive signals for growth = PROTO-ONCOGENES Negative signals for growth = TUMOR SUPPRESSOR GENES

THEREFORE: ↓tumour-suppressor genes + ↑proto-oncogenes = cancer

ITS ALL ABOUT INHIBITING THE BAX PROTEIN: ↑p53 = ↑BAX = Apoptosis BAX: – goes into mitochondria

– ↓mitochondria H+ potential

– thus, ↓ATP production

– thus, release of Cytochrome C and AIF ( Apoptosis Inducing Factor) – thus, caspase cascade – which results in endonuclease being expressed – ENDONUCLEASE shreds the DNA; thus, cell is dead.

GROWTH FACTORS: Progression though this cycle is driven by cyclin-dependant kinases; G zero phase = loss of cyclin stimulus

To exit G zero phase, cells need a cell-specific growth factor to trigger cyclin production

PATHWAY: Hormone � membrane G protein � Kinase cascade (MAPKKK, MAPKK, MAPK)�Transcription factor for cyclin

MITOSIS

Are chromosomes separated? Attempts at repair or apoptosis

G zero phase (quiescense)

G2 Phase DNA replication complete? NO= apoptosis Cell growth: appropriate size? No= apoptosis

G1 phase

Survival factors? None=apoptosis Growth factors? None= cannot progress to S phase Anchorage lost? =apoptosis

S Phase

ATTACHMENT/ANCHORAGE FACTORS: Integrin membrane proteins interact with extracellular matrix, and signal the cell to say that its still anchored via the Focal Adhesion Kinase � RAF � DNA POLYMERASE (needed for mitosis) BUT: Cells will not reproduce if ALL the surfaces are anchored (i.e. surrounded on all sides by other cells) SURVIVAL FACTORS – block apoptosis by inhibiting BAX – activate p13 kinase: – P13 regulates MDM2; – MDM2 shuttles p53 out of the nucleus: this means “Don’t Panic, all is well”

DNA REPLICATION / DAMAGE FACTORS: @ G2���� M phase – Sensor proteins BIND TO DNA – In event of error they…

– Activate kinases ATM and ATR – ATM and ATR phosphorylate p53 (this is the “PANIC!” signal) – p53 binds to DNA, drives transcription of BAX and AIF – p53 also drives transcription of p21 which inhibits CYCLIN; therefore = no command to grow

HORMONAL INFLUENCES ON BREAST CANCER: Factors which influence cell growth:

– ENDOCRINE: circulate in serum, eg. estrogen

– PARACRINE: local, secreted by neighbour cells eg. IFNα, fibroblast growth factor – AUTOCRINE: secreted by the cell itself, into itself.

MALIGNANT CELLS TEND TO LOSE THEIR RELIANCE ON ENDOCRINE GROWTH FACTORS

(if every other checkpoint broke down, why not this one) ESTROGEN IN BREASTS:

– Stimulates Growth and Development of female genitals and breasts during puberty – Promotes ductal cell development – Closes long bone growth plates – Reduces blood choloesterol – Inhibits calcium resorption in bone

CONTROL OF ESTROGEN PRODUCTION:

GnRH (Gonadotropin Relesing Hormone)-via portal veins

FSH (Follicle Stimulating Hormone) –into general circulation

In the ovaries: ESTROGEN is produced in response to FSH; out of Testosterone

in males, produced by fat cells.

PROPERTIES OF ESTROGEN: – Non-Water-Soluble (readily soluble in lipids) – In plasma, carried by SEX HORMONE BINDING GLOBULIN (SHBG) – Diffuses easily into the cell where it binds to Estrogen Receptor in the cytoplasm

ESTROGEN RECEPTROS: two types: Alpha and Beta (ALPHA MOST IMPORTANT TO BREAST CANCER)

– Receptors shuttle between cytoplasm and nucleus – Estrogen-bound form of receptor penetrates the nucleus via a nuclear pore, “docking protein” and then

– DIMERISES – TRANSLOCATES – Searches for an Estrogen Response Element in the DNA with “zinc fingers” – Finding it, binds and immobilises – Switches on the production of growth factors

THUS: IF a cancer is tested ER positive (or Progesterone Receptor, PR positive), it will not grow if Tamoxifen binds the receptor

TAMOXIFEN IS NON-STEROIDAL still allows some estrogen effects in the uterus because it permits some growth factor transcription.

STEROIDAL ER blockers tend to have a TOTAL ANTI ESTROGEN EFFECT over the entire body

HYPOTHALAMUS

ANTERIOR PITUITARY

OVARY (follicles)

TARGET TISSUE

CANCER PATHOLOGY Benign: – will remain localised, – cannot spread to other sites, – composed of well differentiated cells that resemble closely their normal counterparts. Dysplasia: – disorderly, but non-neoplastic proliferation – loss in the uniformity of individual cells, – loss in their architectural orientation. – Dysplastic cells also exhibit pleomorphism and large hyperchromatic nuclei: – mitotic figures are again more abundant than usual.

– When dysplastic changes are marked and involve the entire thickness of the epithelium, without

invasion of the basal membrane, the lesion is referred to as carcinoma in situ Malignancy: – implies that the lesion can invade and destroy adjacent tissue and structures, and spread to distant sites (metastasise)

Those composed of undifferentiated cells are ‘anaplastic’. Anaplastic cells: – display marked pleomorphism (large variation in size and shape). – Characteristically the nuclei are extremely hyperchromatic and large, and variable in shape – Mitoses are often numerous and atypical and anaplastic cells usually fail to develop patterns of orientation to one another.

Cancers grow by progressive infiltration, invasion, destruction and penetration of the surrounding tissue, and do not develop well defined capsules. Next to the development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumours METASTASIS: 1. Seeding: where neoplasms invade a natural body cavity 2.Lymphatic spread: this is the favoured pathways of carcinomas 3.Hematogenous spread: favoured by sarcomas, arteries are generally less penetrated than veins PATHOLOGICAL APPEARANCE: MACROSCOPIC:

– crab-like invasion pattern – “Claws” penetrate along connective tissue boundaries

(path of least resistence = common theme in cancer spread) – Calcified ducts, “pear-like” texture- like a cut fruit – Fibrous tissue is abundant – Fascial planes limit growth …for a while

MICROSCOPIC: – Areas of great nuclear density of breast tissue- HYPERCHROMATIC

SUBSPECIES OF BREAST CANCER: Microscopic Appearance and NOT ORIGIN dictates the name Below: ASPIRATION OF BREAST CELLS:

INFILTRATING BREAST CARCINOMA

Breast carcinoma which has spread to lymph node

SUBSPECIES OF BREAST CANCER: HISTOLOGICAL FEATURES DUCTAL CARCINOMA:

– Papillary: – nuclei are hyperchromatic – cribiform pattern of fused papillae – monomorphic cells – scant stroma – no inflammation around tumour

– Medullary: – Clusters of large polygonal cells – Abundant lymphoid infiltrate

– Mucinous: – Small cells – Clumps surrounded by mucin – Surrounded by thin connective tissue

– Tubular: – Well-differentiated but chaotic tubules – Absence of anaplasia

LOBULAR CARCINOMA:

– Hyperchromatic nuclei

– Small cells in concentric circles around ducts

Relevant anatomy: the BREAST -is composed of: Lactiferous Sinuses (x 6-10) Lactiferous ducts (branches from sinus) Segmental Ducts (inside lobe segments) Terminal Ducts (inside lobules) Acini (sing. Acinus) which are the end of the line All segments are the whole breast All lobules are one segment Coopers ligaments may become pulled or distorted by the cancer: therefore you get dimpling, nipple retraction etc THE LYMPHATIC SYSTEM: – Removes excess extracellular fluid, particulate

matter and proteins from tissue spaces- returns it to the blood (2/3rds of it from Liver and Intestines)

– Abundant in exterior contact tissue – Limited in muscles, bones, fascia – None in CNS, bone marrow, avascular tissue

Flow with valves but no pump: movement is actuated by muscle/body movements, massage etc.- PRIMARY FORCE = -ve pressure in the Thorax Av. Rate = 120 ml/hr ANYTHING BELOW UMBILICUS drains into

INGUINAL NODES;

ANYTHING ABOVE UMBILICUS drains into

AXILLARY NODES

ALL LYMPH eventually drains through the thoracic duct into the superior vena cava where it will return to the circulation. THE BREAST DRAINS…:

– 75% ant. Axillary nodes

(axillary tail, behind pectoralis muscle)

– also supraclavicular, deep cervical

nodes; contralateral breast, internal

thoracic or mediastinal nodes and

abdominal wall.

Behavioural science ############################################### Dealing with the Diagnosis: Cancer usually comes as a shock.

Cancer patients do not change dramatically, but rather go on coping in the same way that they have previously coped.

(personality remains the same) THEREFORE If they have maladaptive coping patterns in the past, these tend to persevere.

HOWEVER if they have been operating in the dominant and loving quadrant in the past, (see Tim

Leary) they tend to take responsibility for their illness and to find out about the illness.

After diagnosis, many patients feel angry, frightened, and confused

-blame themselves, stress, or environment for their "catching" cancer.

Denial is a common reaction.

Patients are strongly advised to seek psychological counselling or therapy upon diagnosis, as this has

been shown to increase 5 year survival rates. Diagnosis and treatment are essential for the individuals to

cope successfully with the disease. Otherwise, there is likely to be increased suicide risk, reckless and

irrational behavior, and non-compliance with treatment

* Average survival time for women in the support groups was 36.6 months. (!!!)

* Average survival time for women with no psychotherapy was 18.9 months (Within four years of the study, ALL of the women with no psychotherapy had died. Ten years after the study, two women who attended therapy

groups were still alive!)

– Post-diagnosis many people may have symptoms of anxiety and depression

that may meet the criteria for Acute Stress Disorder (ASD).

– Their fear and helplessness may lead to

– dissociative experiences,

– recurrent nightmares of first hearing the diagnosis,

– avoidance of all references to cancer,

– anxiety-related sleep problems,

– irritability,

– poor concentration, and

– hypervigilance

A strong support system is thought to bolster the immune system.

In one study, women with terminal breast cancer who belonged to a support group

lived twice as long as those who did not.

Personality type has no impact on 5 year survival length, and neither does stress.

ATHEISM seems to have a NEGATIVE IMPACT on cancer pt. survival

Middle Adulthood: Stage 7 of Erikson’s eight stages (35-65 yrs): RESOLVES THE ISSUES OF - GENERATIVITY (guiding the next generation)

- vs. STAGNATION (concern with own needs) -how this is resolved depends on personal strength to produce for and care for other people Erikson and Freud both admit that LOVE AND WORK are the major tasks of adulthood

(McClelland) ���� MOTIVATION TO ACHIEVE: stable characteristic of personality:

driven by DESIRE FOR POSITIVE AFFECTIONATE RESPONSES

MASLOW THEORY: “Pyramid of Needs”- Ideal of SELF-ACTUALISATION

Bottom: - Biological needs (food, shelter)

- Safety needs (desire to feel secure)

- Love needs (belongingness, need to affiliate with others)

- Esteem needs (desire to achieve goals and confidence in one’s own self)

Top: - Self-Actualisation

Self-actualisation means being

- Fully Human

- Capable of making choices

- Choosing to grow - Awareness of who they are, what they are, what they like, what they don't

like, what is good and bad for them, where they are going, and what their mission is

- Ability to identify their use of psychological defences and have the courage to determine which are adaptive and maladaptive

Mid-life crisis IS NOT a valid or useful way of thinking about how people progress through their life.

Crises are spread out throughout life; women in their thirties have more crises then in forties

Relationships in middle adulthood Harry Stack Sullivan distinguishes three facets of the love relationship

- Lust - the desire for sex.

- Security - the component of a relationship which affirms and confirms the identity of the other person.

Often when people are developing and seeking identity, they can be greatly helped by other

individuals whom they respect and who are close to them and who affirms and help them confirm who

they are.

- Intimacy - as a deep, caring relationship that can be open, respectful, and supportive

with an exchange of confidence in western societies, people think that all three facets of love can be found in one person, the marriage partner

Timothy Leary: circumplex model of interpersonal relationships

(based on a statistical analysis of all the dictionary terms for interpersonal relationships.)

Two main axes emerged:

- dominant-submissive

- hateful-loving in a relationship if there is dominance being expressed by one partner, then the other partner may have to be correspondingly submissive, …BUT not necessarily in every aspect of the relationship – the balance of power may vary in different situations and roles. Difficulties can arise when either both are submissive, or both are dominant most of the time.

hateful-loving: people who advance a loving or friendly posture are more likely to elicit and invoke friendly, positive responses a hateful, attacking overture in relationships is more likely to arouse a pugnacious response in the other individual IN DISEASE, a patient may not be able to function in their usual role: eg. abandon their usual independence / leadership and become over-dependant THUS: identify how a patient is operating interpersonally, and to try to change their predominant interactional mode to suit their position better.

Women, middle age and health Personality and stress

- In Australia, women live longer than men, - have higher rates of acute and chronic illness, - use health care services more frequently. strong evidence that various personality traits mediate stress reactions and correspondingly affect immune responses positively or negatively. Personal traits that help in stressful situations:

- hardiness,

- ability to confide in others,

- ability to recognise and express feelings,

- assertiveness,

- complex multiple roles :

(so that if one role "fails" another can be a source of satisfaction and self-esteem).

Women in traditional female areas of employment report more physical health problems

-not merely poor women

Major stressors reported by women include • managing home responsibilities

• not receiving adequate emotional support or help from their partner

• not having time to relax

• anger and depression

• low paying and unrewarding jobs THUS: determine personality traits, stress responses, levels of social support, - then assist with coping via cognitive and behaviour therapies

Cognitive factors in adulthood

post-formal thought: sophisticated adult reasoning

• New abilities

• More concrete and pragmatic cognitive, less idealistic approaches

• Being able to see relative relationships between classes of objects, not just absolute criteria

• Being able to accept contradictions !!! INTELLECTUAL EFFICIENCY IS POSITIVELY CORRELATED WITH GOOD HEALTH !!!

the strongest independent predictor of health

Genetics Breast cancer Prevalence Genes: BRCA-1 and BRCA-2; increase chances to 80%

-about 1% of all breast cancers; 1 in 1000 women. THAT’S WHY WE DON’T SCREEN FOR IT

Pharmacology Tamoxifen:

Tamoxifen (Nolvadex®) is a medication in pill form.

used as adjuvant, or additional, therapy following primary treatment for early stage breast cancer.

In women at high risk, tamoxifen reduces the chance of developing the disease.

adding tamoxifen significantly reduced the incidence of all invasive and non invasive breast cancers at

any site by 37%,

Patients with hormone sensitive tumors who get chemotherapy combined with Tamoxifen should probably

have the Tamoxifen held until after the chemotherapy is completed

CHEMO: Currently considered standard chemotherapy:

FAC (fluorouracil, doxorubicin, and cyclophosphamide; Six cycles of duration 18-24 weeks) or

FEC (fluorouracil, epirubicin, and cyclophosphamide; six cycles of duration 18-24 weeks), or

CMF (six cycles, duration 18-24 weeks), or

AC (four cycles, doxorubicin and cyclophosphamide, duration 12 to 16 weeks)