Breast Cancer Flashcards
Breast cancer is the most common form of malignancy in women, especially in those aged over ____ years
50
What are the risk factors for developing breast cancer? (8)
- Age over 50
- Early onset of menstruation
- Late menopause
- Older age at first completed pregnancy
- Family history of breast cancer
- Use of OCP and/or HRT
- Obesity
- Alcohol consumption
*factors that increase estrogen exposure
Breast cancer in men is rare. Although risk factors are not fully understood, it may be associated with abnormalities of sex hormone metabolism, including those caused by ____________ or _____________, genetic predisposition, and environmental risk factors such as industrial exposure to _______________
liver diseas
testicular trauma
chronic heat
What factors protect against breast cancer? (2)
- Physical activity
2. Breast feeding
Non-invasive breast cancer, also known as ____________, is when the cancer remains localised in the ducts
ductal carcinoma in situ
*However, in most cases, the cancer is invasive at the time of diagnosis, which means that malignant cells are liable to spread beyond the immediate area of the tumor
What is the staging of breast cancer?
- Early (stage I/II)
- Locally advanced (stage III)
- Advanced (stage IV)
At what age does breast cancer screening begin in the UK?
50 until 71 yo every 3 years
https://www.nhs.uk/conditions/breast-screening-mammogram/when-youll-be-invited-and-who-should-go/
Surgery and radiotherapy aim to _______________, whilst adjuvant drug therapy (drug treatment following surgery) aims to _________________
remove the tumour mass
reduce the risk of disease recurrence and the risk of developing invasive disease
What is the aim of neoadjuvant drug therapy?
Neoadjuvant drug therapy (drug treatment before surgery) aims to reduce the size of the tumour to allow breast-conserving surgery to be possible and to reduce axillary lymph node involvement
Is advanced breast cancer curable?
No; aim of treatment is to prolong survival, relieve symptoms of disease and improve QoL
The management of patients with breast cancer involves ______________, _____________, ____________, or a combination of these
surgery
radiotherapy
drug therapy
What factors determine the extent and aggressiveness of breast cancer? (5)
- Patient age
- Menopausal status
- Tumor size and grade
- Involvement of axillary LNs or skin
- Presence of hormone receptors within the tumor
What is the treatment of early or locally advanced breast cancer?
These cancers are considered operable; therefore the treatment involves:
- surgery to the breast (breast-conserving surgery or mastectomy) and to the axillary lymph nodes
+/- radiotherapy to reduce local recurrence rates
+/- often followed by adjuvant drug therapy to eradicate micro-mets that cause relapses
In women with ____________ breast cancer, radiotherapy is recommended after breast-conserving surgery with clear margins (no cancer cells are found at the edges of the removed tissue), as it reduces local recurrence rates
invasive
In women with invasive breast cancer, ______________ is recommended after breast-conserving surgery with clear margins (no cancer cells are found at the edges of the removed tissue), as it reduces local recurrence rates
radiotherapy
*However, the use of radiotherapy may be omitted if risk of local recurrence is very low and the woman is willing to take adjuvant endocrine therapy for a minimum of 5 years
______________ is also recommended after mastectomy in patients with node-positive invasive breast cancer or involved resection margins (cancer cells are found at the edges of the removed tissue)
Radiotherapy
In which cases of early and locally advanced breast cancer is post-operative radiotherapy recommended? (3)
- Invasive breast cancer treated with breast-conserving surgery with clears margins
- After mastectomy in patients with node-positive invasive breast cancer OR with involved resection margins
- Patients with node-negative T3 or T4 invasive breast cancer
Adjuvant drug therapy following treatment of breast cancer includes… (4)
- Chemotherapy
- Endocrine therapy
- Biological therapy
- Bisphosphonate therapy
What factors affect the decision to use adjuvant drug therapy? (3)
- Risks and benefits of treatment
- Disease prognosis
- Predictive factors such as ER/PR/HER2 status of the primary tumor
Adjuvant ____________________ combination chemotherapy is recommended in patients with invasive breast cancer who are at sufficient risk of disease recurrence to require chemotherapy
anthracycline–taxane
Which biological therapy is typically offered in the adjuvant treatment of invasive breast cancer?
Trastuzumab (aka Herceptin); monoclonal antibody that binds to HER2 receptors leading to preferential cell death
Herceptin is also called ______________
Traztuzumab (monoclonal ab against HER2)
_____________ function should be regularly assessed in patients receiving trastuzumab, and particular caution should be taken in patients with underlying _____________ disease (consult product literature for further details)
Cardiac
cardiac
What hormonal therapies are used in the treatment of breast cancer?
Tamoxifen (men and pre- and perimenopausal women)
Anostrazole (post-menopausal women)
Trastuzumab cannot be used in patients with a history of ___________ disorders
heart
What is the objective of hormonal therapy in the treatment of breast cancer?
Antagonism of estrogen in ER+ cancers through:
- blockage of estradiol receptor sites (tamoxifen, a SERM with antagonist and agonist activity) OR
- suppression of estrogen production (anostrazole, an aromatase inhibitor)
Why is anastrozole preferentially used in the treatment of breast cancer in post-menopausal women?
Aromatisation or adrenal androgens accounts for the majority of estrogen production in post-menopausal women (vs ovarian production in premenopausal women)
*vs tamoxifen which has partial estrogen agonist properties and therefore does not suppress it as effectively
Hormonal therapy is only used in _________+ breast cancers
Estrogen (ER+)
In addition to tamoxifen therapy, ovarian function suppression with a _______________ should be considered in premenopausal women, taking into account the risk of temporary menopause.
gonadotropin-releasing hormone (GnRH)
- Ovarian function suppression aims to stop the production of circulating oestrogen, which can stimulate breast cancer progression
In postmenopausal women with oestrogen-receptor positive invasive breast cancer who are at medium or high-risk of disease recurrence, a(n) _______________ should be given as first-line therapy. Alternatively, ______________ should be given if a(n) _________________ is not tolerated or is contra-indicated, or if the risk of disease recurrence is low.
aromatase inhibitor
tamoxifen
aromatase inhibitor
Endocrine therapy for ER+ breast cancer typically lasts up to _____ years; endocrine therapy beyond this is considered ____________ and is unlicensed
5
Extended
*still, NICE recommends that anastrozole should be offered to postmenopausal women with oestrogen-receptor-positive invasive breast cancer at medium or high-risk of disease recurrence who have been taking tamoxifen for 2 to 5 years. Extended therapy should also be considered in postmenopausal women at low risk of disease recurrence
Following breast-conserving surgery, endocrine therapy should be offered to women with oestrogen-positive ductal carcinoma in situ, if ________________ is recommended but not given. If radiotherapy is not recommended, the use of endocrine therapy should also be considered
radiotherapy
Following breast-conserving surgery, ___________ therapy should be offered to women with oestrogen-positive ductal carcinoma in situ, if radiotherapy is recommended but not given. If radiotherapy is not recommended, the use of endocrine therapy should also be considered
endocrine
________________ and ______________ have been shown to improve disease-free survival and overall survival in postmenopausal women with node-positive invasive breast cancer
Zoledronic acid
sodium clodronate
- However, there is insufficient evidence to recommend their use in premenopausal women
Is bisphosphonate therapy recommended as part of adjuvant therapy in premenopausal women with breast cancer?
Insufficient evidence to recommend its use
Intravenous zoledronic acid [unlicensed indication] or oral sodium clodronate [unlicensed indication] should be offered to postmenopausal women with ________________ breast cancer.
lymph-node-positive invasive
- Treatment should also be considered in those with lymph-node-negative invasive breast cancer who are at high-risk of recurrence
Bisphosphonate therapy is also recommended in women at high-risk of osteoporosis due to the use of ________________ in postmenopausal women, or in women with _________________
aromatase inhibitors
treatment-induced premature menopause
Neoadjuvant drug therapy may involve the use of ______________ or _____________ therapy
chemotherapy
endocrine
Neoadjuvant chemotherapy should be offered to reduce tumour size in patients with ________________ invasive breast cancer
oestrogen-receptor-negative
In patients with oestrogen-receptor-positive invasive breast cancer, chemotherapy should be considered. In patients with HER2-positive invasive breast cancer, neoadjuvant chemotherapy should be offered in combination with trastuzumab and pertuzumab
A chemotherapy regimen containing both a ______________ and an ______________ should be considered in patients with triple-negative invasive breast cancer (oestrogen-receptor-negative, progesterone-receptor negative and HER2-negative)
platinum [unlicensed indication]
anthracycline
If chemotherapy is not indicated, neoadjuvant _____________ therapy should be considered as an alternative in postmenopausal women with oestrogen-receptor-positive invasive breast cancer
endocrine
Chemotherapy and endocrine therapy are equally effective in postmenopausal women in terms of _____________ and ____________
breast-conservation
shrinking of the tumour
Although chemotherapy is more effective than endocrine therapy at shrinking the tumour in _____________ women, some tumours may respond to endocrine treatment
premenopausal
Although ______________ is more effective than ______________ therapy at shrinking the tumour in premenopausal women, some tumours may respond to endocrine treatment
chemotherapy
endocrine
What is the first line treatment of ER+ advanced breast cancer?
Endocrine therapy
____________ should be offered to pre- and perimenopausal women who have had disease progression despite treatment with tamoxifen
Ovarian function suppression
Ovarian function suppression should be offered to pre- and perimenopausal women who have had disease progression despite treatment with _____________
tamoxifen
What is the first line treatment of ER+ advanced breast cancer in men?
Tamoxifen
______________ should be offered as first-line treatment in patients with oestrogen-receptor-positive advanced breast cancer that is imminently life-threatening or requires early relief of symptoms because of significant visceral organ involvement
Chemotherapy
- Once chemotherapy treatment is completed, endocrine therapy should be offered
Chemotherapy should be offered as first-line treatment in patients with oestrogen-receptor-positive advanced breast cancer that is imminently life-threatening or requires early relief of symptoms because of significant visceral organ involvement. Once chemotherapy treatment is completed, _____________ therapy should be offered
endocrine
Trastuzumab is recommended for the treatment of HER2-positive advanced breast cancer. It is used in combination with ____________ in those who have not received chemotherapy for metastatic breast cancer, and as monotherapy for patients who have received at least two chemotherapy regimens for metastatic breast cancer
paclitaxel
The use of bisphosphonates should be considered in patients with metastatic breast cancer to ____________ and ____________ of bone metastases
reduce pain
prevent skeletal complications
_____________ should be offered to all women who have been identified as being at high- and moderate-risk of developing breast cancer
Chemoprevention eg familial breast cancer
Other strategies to reduce breast cancer risk should also be considered, for example ___________ or ___________
bilateral mastectomy
bilateral oophorectomy
Should women who are at high risk of breast cancer who have undergone bilateral mastectomy receive chemoprevention?
No
Chemoprevention should only be continued for ____ years
5
_____________ is recommended as chemoprevention for premenopausal women who do not have a history of, or increased risk of thromboembolic disease or endometrial cancer
Tamoxifen
In women who have severe osteoporosis, or who do not wish to take anastrozole, treatment with _________________ can be given, provided there is no history, or increased risk of thromboembolic disease or endometrial cancer
tamoxifen
In women who have severe osteoporosis, or who do not wish to take anastrozole, treatment with tamoxifen can be given, provided there is no history, or increased risk of __________________ or _________________
thromboembolic disease
endometrial cancer
Alternatively, _________________ is an option [unlicensed indication] in postmenopausal women with a uterus who do not wish to take tamoxifen, unless there is a history or increased risk of thromboembolic disease
raloxifene hydrochloride
Alternatively, raloxifene hydrochloride is an option [unlicensed indication] in postmenopausal women with a uterus who do not wish to take tamoxifen, unless there is a history or increased risk of __________________
thromboembolic disease
Some treatments used in the management of breast cancer, such as tamoxifen or ovarian function suppression may lead to _______________, and women should be counselled about these side-effects prior to starting any of these treatments
menopausal symptoms or early menopause
Some treatments used in the management of breast cancer, such as ________________ or __________________ may lead to menopausal symptoms or early menopause, and women should be counselled about these side-effects prior to starting any of these treatments
tamoxifen
ovarian function suppression
Women diagnosed with breast cancer should discontinue their ________________ because of possible tumour stimulation and interference with adjuvant endocrine therapy
hormone replacement therapy (HRT)
____________ should not be offered routinely to women with menopausal symptoms if they have a history of breast cancer
HRT; however, in exceptional circumstances, HRT can be offered to women with severe menopausal symptoms once the associated risks have been discussed
_____________ may be offered to relieve menopausal symptoms such as hot flushes in women with breast cancer who are not taking tamoxifen
Selective serotonin re-uptake inhibitor (SSRIs) antidepressants
_______________, _______________ [unlicensed indication] and _______________ [unlicensed indication] are sometimes used for the treatment of hot flushes in women with breast cancer after discussion with the patient and information given about side effects
Clonidine hydrochloride
venlafaxine
gabapentin
(However, SSRIs are preferred)
________________ is an anti estrogen which induces gonadotrophins release by occupying estrogen receptors in the hypothalamus, thereby interfering with feedback mechanisms
Tamoxifen
Tamoxifen is contraindicated in patients with a history of _________________ or genetic predisposition to ______________
VTE
Thromboembolism
What are the common or very common side effects of tamoxifen? (17)
- Alopecia
- Anemia
- Cataracts, retinopathy
- Cerebral ischemia
- Constipation, diarrhea, nausea
- Dizziness, fatigue
- Embolism and thrombosis
- Fluid retention
- Headache
- Hepatic disorders
- Hot flushes
- Hypersensitivity, skin reactions
- Hypertriglyceridemia
- Muscle complaints
- Neoplasms
- Uterine disorders, vaginal hemorrhage, vulvovaginal disorders
- Altered taste, abnormal sensation
What are the main 2 side effects that must be considered when prescribing tamoxifen?
- Endometrial changes including hyperplasia, polyps, and cancer
- Thromboembolism, particularly when used during or immediately after major surgery or periods of immobilization
Unless being used in the treatment of female infertility, effective contraception must be used during treatment with tamoxifen and for ____ months after stopping
2
Is tamoxifen safe to use during pregnancy and breastfeeding?
Avoid during pregnancy due to possible effects on fetal development
Avoid during breastfeeding due to suppression of lactation
Traztuzumab therapy is contraindicated in patients with _____________
Severe dyspnea at rest
Manufacturer advises effective contraception in women of childbearing potential during and for _____ months after treatment with traztuzumab
7
Is trastuzumab safe to use during pregnancy and breastfeeding?
Avoid in both - Oligohydramnios reported
Avoid during breastfeeding and for 7 months afterward
What are the monitoring requirements for patients taking trastuzumab?
Monitor cardiac function before and during treatment
Is trastuzumab interchangeable with trastuzumab emtansine or trastuzumab deruxtecan?
NO; Biological medicines must be prescribed and dispensed by brand name
What is the main contraindication of anastrozole?
Premenopausal women
Anastrozole should be prescribed with caution in which patients?
Patients with susceptibility to osteoporosis
What are the common or very common side effects of anastrozole? (12)
- Alopecia
- Decreased appetite, diarrhea, N/V
- Arthritis, bone pain, carpal tunnel syndrome, joint disorders, myalgia
- Asthenia
- Drowsiness
- Headache
- Hot flushes
- Hypercholesterolemia
- Hypersensitivity
- Osteoporosis
- Abnormal sensation, taste altered
- Vulvovaginal dryness, vaginal hemorrhage
Is anastrozole safe to prescribe in patients with hepatic and/or renal impairment?
Caution in moderate to severe impairment
Caution if eGFR is less than 30
What pre-treatment screening should be performed before prescribing anastrozole?
Lab test for menopause if in doubt
What are the monitoring requirements for patients taking anastrozole?
Assess bone mineral density before treatment and at regular intervals
What advice should be given to patients and carers regarding anastrozole?
Asthenia and drowsiness may affect ability to drive or operate machinery
What is the mechanism of action of raloxifene?
A SERM: agonist at bone, antagonist at breast tissue
Prevents and treats osteoporosis by mimicking the effects of estrogen to increase bone density
Also decreases the risk of developing invasive breast cancer by blocking the effects of estrogen on breast tissue
What are the contraindications for raloxifene use? (4)
- Cholestasis
- Endometrial cancer
- History of VTE
- Undiagnosed uterine bleeding
What are the common or very common side effects of raloxifene? (4)
- Influenza
- Leg cramps
- Peripheral edema
- Vasodilation
(Less commonly embolism and thrombosis)
Can raloxifene be used in hepatic and/or renal impairment?
Avoid in hepatic impairment and severe renal impairment
Caution in mild to moderate renal impairment
