Breast Cancer

Breast cancer is a diverse and heterogenous disease. Over the years due to increased understanding of the pathophysiology and genetic drivers treatment has become more and more individualised.

Over the following sections I will highlight useful learning resources as well as links to relevant papers. I hope to provide a basic overview of treatment that is required for successful sitting of the FRCR exams.

Anatomy

Breasts

- Extend from 2nd to 6th rib

- consist of 4 quadrants and a central portion. 50% occur in UOQ and these have best prognosis.

- lymphatic drainage to axillary nodes and internal mammary which lie alongside the internal thoracic artery

link to radiopaedia for more detail on breast anatomy

Axillary nodes

  • level I: below the lower edge of the pectoralis minor muscle
  • level II: underneath/posterior the pectoralis minor muscle
  • level III: above/medial the pectoralis minor muscle

link to radiopaedia for more detail on axillary node anatomy

Staging

AJCC 8th ed
AJCC
AJCC 8th ed

Pathology

Almost all are adenocarcinoma.

Graded according to Nottingham grading system - G1, 2 or 3

ER and PR

Assessed by IHC. ER more common in post-menopausal, <50% of pre-menopausal.

Allred score combines a score based on % of positive cells and intensity of reaction. Gives a score out of 8 with 0 and 2 considered negative.

About 20% of ER neg tumours are PR pos – reasons include a low level of ER expression or a false negative ER result. Account for 5% of all tumours and are likely to respond to hormone treatment.

HER2

Can be assessed by IHC with 3+ pos. if 2+ then confirm by measuring number of gene copies with FISH (positive if HER2/CEP17 ratio >2 by ISH or HER2 copy number >6 regardless of ISH (if copy number 4-6 then this is equivocal and needs alternative ISH)).

Molecular subtyping

Identifies 4 different subtypes and these correlate with prognosis

- Luminal A; ER/PR pos, low Ki67 (G1-2), molecular marker ‘favourable’

- Luminal B; ER pos/PR low, Ki67 high (G3), molecular marker ‘unfavourable’

- HER2 pos; ER/PR pos or neg, generally G3

- Basal like; Triple neg, generally G3

Gene expression patterns of breast carcinomas
Sorlie et al
PNAS 2001

Original paper describing the 4 molecular subtypes of breast cancer

Screening and Assessment

Screening

  • In the UK between 50-70 yrs old every 3 yrs.
  • Mammogram with mediolateral oblique and cranio-caudal.
  • Recall rate is 4% with 1% going on to biopsy most of whom will have either invasive or in-situ disease.

If assessed as being at high or moderate risk (>17% lifetime risk) may be offered annual MMG or MRI scanning according to age and risk category.

- Aged 40-49; annual MMG

- Aged 30-49 if known or >30% risk of BRCA; annual MRI

- Age 20-49 if Li-Fraumeni(TP53); annual MRI

Assessment

  • Triple assessment – P(physical exam), M (MMG), U (USS) and C (cytology)/B(biopsy).
  • All scored 1-5 with 1=inadequate, 2= benign, 3= suspicious probable benign, 4=suspicious probably malignant and 5= malignant.
  • If T3 or N2 then need staging for metastatic disease such as CT CAP and bone scan. In T3> up to 15-20% incidence of M+.
  • If T2N1 only do distant staging if reasons to be concerned – symptoms/abnormal bloods.
  • Consider PET in locally advanced disease IIIB+ to look for distant disease especially patients with inflammatory breast cancer.

Surgery

General principles

Breast surgeons should follow the Oncoplastic Breast Reconstruction Guidelines for Best Practice

Patients should be treated by an oncoplastic team (oncoplastic unit or centre); units that do not have oncoplastic breast surgery on site should seek to establish a patient pathway that is in line with these guidelines.

Where surgery is the first treatment, this should take place within 31 days of the diagnosis being made. In medically fit patients, non-reconstructive breast cases should be done as day-case/23-hour surgery.

Patients should have all surgical options which may apply (breast conservation, mastectomy with or without reconstruction and, if appropriate, oncoplastic conservation procedures) discussed with them in the presence of their key worker/clinical nurse specialist (CNS).

The patient’s choice must always be respected.

The National Mastectomy Audit reported unacceptable levels of pain in women having mastectomy alone or mastectomy plus reconstruction. Protocols should exist to manage and assess post-operative pain in these patients.

Choice of breast operation

Surgery may be the initial treatment or it may be undertaken after primary chemotherapy or endocrine therapy. The same principles will apply in either case. The majority of cases will be suitable for breast conservation. However, it is important to ensure that conservation surgery will leave the patient with an aesthetically acceptable breast (preserved breast shape and well placed scars).

Indications for mastectomy:

  • Unfavourable tumour: breast volume ratio (i.e. a large tumour in a small breast). In these circumstances, consideration should be given to oncoplastic resections (therapeutic mammoplasty, Grissoti flap or round block resections). If these techniques are not available locally, patients should be given the option of referral to an oncoplastic surgeon. Also consider downsizing the tumour with primary medical treatment.
  • Where there is a recurrent tumour in a breast that has previously been irradiated with whole breast radiotherapy.
  • Where radiotherapy may be contraindicated – excessive photosensitivity, vasculitis, severe pulmonary fibrosis, scleroderma, previous mantle radiotherapy. Previous mantle radiotherapy is not an absolute indication for mastectomy and breast conservation with partial breast radiotherapy should be discussed with the patient as an alternative.
  • Where there is extensive ductal carcinoma in situ (DCIS) of high or intermediate grade. If there is extensive low grade DCIS, the patient should be informed of the uncertainty over the natural history of low grade DCIS. Observation may be considered within the context of a clinical trial such as the LORIS trial. Consideration should also be given to biopsy of more than one focus of microcalcification prior to proceeding with mastectomy. A second biopsy should ideally be taken from the edge of suspected extent.
  • Where there are multifocal/multicentric tumours, whether invasive or non-invasive. In some circumstances, oncoplastic techniques may obviate the need for mastectomy and can be considered

Breast reconstruction

  • All patients for whom mastectomy is a treatment option should have the opportunity to receive advice on breast reconstructive surgery. Not all patients will be physically fit for or wish to consider reconstruction. The reason a patient declines or is advised against immediate breast reconstruction (IBR) should be recorded. IBR rates will be compared across Trusts and should not be lower than national average.
  • For patients who express an interest in breast reconstruction, discussions should take place on the ideal timing of the reconstruction. This should include the risks and benefits of immediate versus delayed breast reconstruction techniques.
  • The full range of suitable reconstructive techniques should be discussed with the patient. These should include tissue expansion/implant reconstruction with or without acellular dermal matrix reinforcement, latissimus dorsi flap reconstruction (autologous or with implant), and free flap reconstruction (muscle- sparing TRAM, DIEP, TMG, SGAP or IGAP).
  • If PMRT is likely, full information regarding the potentially unfavourable longer term impact of radiotherapy on both implants and autologous tissue needs to be discussed and considered.
  • Expanders incorporating metal ports with the radiotherapy field may interfere with radiotherapy planning and dosage and should be avoided.

Management of the axilla

  • Pre-operative staging of the axilla should be undertaken in all invasive cancers using ultrasound and, if indicated, guided fine needle aspiration cytology or core biopsy.
  • If pre-operative staging of the axilla reveals metastases (C5 or B5), a Level II/III axillary lymph node dissection (ALND) should be recommended.
  • If pre-operative staging of the axilla is normal both clinically and on imaging, the axilla should be further staged by SLNB. Patients with abnormal imaging but a normal lymph node biopsy should also be offered SLNB.
  • SLN localisation technique must include radio-isotope as a minimum.
  • In March 2015 the Association of Breast Surgeons (ABS) issued a consensus statement to guide management following a positive sentinel node and this is supported by the RCR postoperative radiotherapy for breast cancer: UK consensus statements published in November 2016.
    • Isolated tumour cells (ITC) and micrometastases: If the sentinel node(s) shows isolated tumour cells and/or micrometastases no further axillary treatment is required in addition to breast conserving surgery or mastectomy.
    • 1–2 positive sentinel nodes with macrometastases: Further axillary treatment is no longer mandatory in patients who are receiving breast conservation with whole breast radiotherapy, who are post-menopausal and have T1, grade 1 or 2, ER positive and HER2 negative tumours. These patients could also be entered into the POSNOC or equivalent clinical trial.
    • Further axillary treatment should be recommended if 3 or more positive sentinel nodes.
    • Further axillary treatment should usually be recommended for patients undergoing mastectomy, or with tumours with one or more of the following features: T3, grade 3, ER- or HER2+. These patients could also be entered into the POSNOC or equivalent clinical trial.

Important papers that are relevant to these current recommendations include;

  • EORTC AMAROS study which randomised patients with T1-2 primary breast cancer and no palpable lymphadenopathy to either axillary radiotherapy or axillary lymph node dissection after a positive sentinel node. Axillary recurrence in both arms was low <1% but due to low event rate study underpowered to statistically meet the non-inferiority test. Lymphoedema at 5 yrs was higher (23%) than in the radiotherapy group (11%).
  • The American Z0011 study randomised patients with T1-2 invasive breast cancer with no palpable lymphadenopathy and 1-2 SLNs were randomised to ALND or no further treatment. All patients underwent lumpectomy and tangential whole breast irradiation. There was no significant difference in survival however criticism of the lack of radiotherapy QA means there is concern regarding the generalisability of the findings to current practice.

The current POSNOC trial is a UK trial which is randomising patients with T1-2 invasive breast cancer and 1-2 SLN to either further axillary treatment (ANC or axillary radiotherapy) or adjuvant therapy alone.


EORTC AMAROS study
Rutgers et al
Lancet oncol 2014

Z0011 study
Giulliano et al
JAMA 2011

POSNOC trial protocol
POSNOC trial group
2017

Radiotherapy

Following breast conserving surgery

Radiotherapy halves the risk of LC among all subgroups of women (EBCTCG 2011) with one cancer death avoided for every 4 recurrences prevented.

If low risk of LR then the absolute benefit is only small. Can use the IBTR online tool at https://www.tuftsmedicalcenter.org/ibtr/ to estimate risk of recurrence and radiotherapy benefit.

  • PRIMEII randomised women >65yrs with T1/2 (up to 3cm) N0 ER+/HER2- breast ca to adj hormones alone or hormonal therapy plus RT. At 5 yrs rate of ipsilateral recurrence 1.3% with RT vs 4.1% without. Authors concluded that RT could be omitted in some.
  • PRIMETIME is currently recruiting women if >60, T1N0, G1-2, ER+/HER2. Using the IHC4+C biomarker to allocate patients as low risk of recurrence to no radiotherapy.

For DCIS

Similar relative risk reduction in recurrence to invasive disease.

Van Nuys Criteria which includes grade, tumour size, margin status and age can help risk stratify.

DCIS lesions with a Van Nuys score of 10-12 are at high risk of local recurrence despite additional radiotherapy and should be considered for re-excision or mastectomy. For other cases, following BCS, RT should be considered as a means of reducing risk of local recurrence as there is no reliable means of identifying a group that derives no or minimal benefit. The VNPI can help define risk, but results should be interpreted with caution.

Role of boost

Reduces risk of LR but at expense of worse cosmesis. EORTC boost trial gave 16Gy/8#. At 10 yrs LC was 10% without and 6% with boost – approx. 40% risk reduction. Absolute benefit greatest if <40 and if at higher risk of recurrence – positive margins, G3, LVI.

RCR consensus statements suggest;

  • A tumour bed boost should be considered for all patients less than 50 years old.
  • A tumour bed boost should be considered for all patients less than 50 years; for those over 50 years with higher risk pathological features (especially Grade 3 and/or extensive intraductal component), consider the benefit of boost in context of both local recurrence and normal tissue toxicity risks.

Following mastectomy

Radiotherapy reduces logoregional recurrence and improves breast cancer mortality (EBCTCG 2015)

Recommend radiotherapy if;

  • pT<50mm
  • >4LNs
  • Excision margin <1mm.

Consider if 1-3 nodes based on reduced recurrence and mortality benefit although in modern era absolute benefits might be smaller.

SUPREMO trial results awaited - randomised women with 1-3 nodes or high risk node negative (T3 or G3 T2) to radiotherapy or not.

Radiotherapy to regional lymphatics

Axilla

See above section on management of axilla

  • If SLNB positive offer further axillary treatment - ALNC/radiotherapy
  • Axillary RT not recommended after complete microscopic clearance due to enhanced risk of treatment related morbidity - axillary RT after ALND significantly increases risk of lymphedema – 38% with both vs 7% with surgery alone).

POSNOC trial is investigating the safe omission of further axillary treatment in patients with 1-2 positive sentinel lymph nodes is women with invasive breast cancer <50mm.

Supraclavicular fossa

Risks of isolated supraclavicular relapse are very low (≤1%) in node negative patients and in some of those with 1–3 positive nodes, but are >15% in women with ≥4 involved axillary lymph nodes.

Therefore recommend radiotherapy;

  • If 4 or more positive axillary nodes

If intermediate risk role less certain. MA20 trial demonstrated no OS at 10yrs but 5% improvement in DFS at expense of higher rate of pneumonitis and lymphoedema. Therefore consider radiotherapy if 1–3 nodes positive and Grade 3 disease as they are at elevated risk of supraclavicular recurrence

Internal mammary chain (IMC)

RT to IMC is increasing but reserved for those at high risk – such as if nodes are known to be involved or 4 or more axillary nodes (ie. N2 disease). Recent RCR consensus statements state that internal mammary nodal radiotherapy should be considered;

  • in patients at high risk of locoregional recurrence (that is, T4 and N2–3 disease) and
  • In patients with 1–3 axillary macrometastases who have been recommended locoregional irradiation based on risk factors, inclusion of the IMC in the target volume should be considered in those with central/medial disease.

Radiotherapy technique and dose, fractionation

Use volunary breath hold technique for all left sided treatments to minimise cardiac dose

Target volume definition

  • See attached ESTRO guidelines for full volume definitions

Whole breast radiotherapy

CTV = glandular breast tissue down to deep fascia.

PTV = CTV +1cm (with 5mm skin sparing)

When using traditional field borders – incorporate visible breast tissue plus 1cm sup and inf then medial to midpoint and laterally to mid axillary line. As rule of thumb max 2cm lung in field or will struggle to meet OAR constraint.

Post mastectomy

Post mastectomy CTV = skin flaps but not muscle or rib cage. Use bolus in those at high risk of skin involvement (positive skin margin/inflammatory ca).

Nodal radiotherapy

- Traditional field border of SCF is; medial- 1cm lateral to midline, lateral coracoid process, sup at least 3cm clear of the medial head of clavicle (approx C7/T1), if including axilla then laterally extended to outer head of humerus with shielding of humeral head and apex of lung provided it doesn't affect coverage of nodal volume. With CT planning if ANC has been performed then often surgical clips can be used to define the lateral border of the SCF field.

Match SCF and breast tangents using half beam block or collimator twist to achieve non divergent edge.

Dose/fractionation

The START trials established 40Gy/15 fractions as international standard and compared to traditional 2Gy/ fraction standard of 50Gy/25 fractions.

FAST trial randomised women >50 with node negative disease to 50/25 or 28.5 in 5 once weekly fractions. With 3 yr fu showing no difference in cosmesis. 10 yr results showed only a handful of recurrences and little difference (approx. 5% more) moderate cosmetic difference at 10 yrs.

FAST-Forward published April 2020 and compared 40/15 with 27/5 or 26/5 over one week in patients with pT1-3 pN0-1 after BCS or mastectomy. 26/5 was shown to be non inferior in terms of local relapse (approx. 2%) and moderate/ marked cosmesis similar (approx 10%). Also have milder early skin reaction.

Therefore for patients who only require radiotherapy to the breast/chest wall;

  • 26Gy in 5 fractions is the new standard.

There was a nodal sub-study within FAST-Forward but this has not yet published therefore if patients also receiving nodal

radiotherapy;

  • 40Gy/15 fractions is sued.

If palliative or fungating especially in the elderly who may struggle with daily treatment then can use 36Gy/6 with once weekly fractionation – review weekly after #4 for skin toxicity.

Planning technique

Breasts are planned with tangential beams with. non divergent posterior edge and matched to an anterior applied nodal field.

Dose constraints

For 26Gy in 5 fractions

Ipsilateral lung V8Gy <15%

Heart – V1.5Gy <30%

For 40Gy in 15 fractions

Ipsilateral lung with nodal field V18Gy<30%

Heart - mean dose <2Gy

Aim to give RT within 8w of surgery as local control possibly compromised if delayed beyond 12w

RCR post operative breast radiotherapy consensus guidelines
RCR
RCR 2016

START trials 10 year follow up
START trialists
START trials 10 year follow up

FAST-Forward trial
Fast forward trialists
Fast Forward trial

PRIME II trial
PRIMEII trialists
Avoidance of RT trial

EBCTCG long term outcome following breast radiotherapy
EBCTCG
EBCTCG long term outcome following breast radiotherapy

EBCTCG post mastectomy radiotherapy long term outcomes
EBCTCG
EBCTCG post mastectomy radiotherapy long term outcomes

ESTRO breast cancer volume atlas
ESTRO
radiotherapy planning

20 yr follow up of EORTC boost study
EORTC
Boost study

Systemic treatment

Neo-Adjuvant

Primary or neo-adjuvant chemotherapy should be considered for patients with:

  • large tumours (≥3cm) that would require a mastectomy
  • locally advanced breast cancer
  • tumours of >2cm in a small volume breast where the multidisciplinary team considers the tumour to be inoperable and operability may be achieved and/or the chance of breast conservation with optimum cosmesis can be significantly improved
  • all women <50 years of age who have ER/PgR/HER2 negative tumours, regardless of tumour size. Systemic chemotherapy is offered as part of the overall management and neo-adjuvant therapy allows additional scope for not only potential downstaging of the tumour but allows women to consider BRCA testing and decision regarding optimal surgery if found to be a mutation carrier. Referral to the genetics service should be made at the start of neo-adjuvant chemotherapy
  • trials in neo-adjuvant chemotherapy may be available.


A relative contraindication to neo-adjuvant chemotherapy being given to avoid mastectomy is the presence of extensive microcalcification at baseline which may prevent conservation after chemotherapy.

A coil marker to define the tumour bed is recommended in patients who are triple negative or HER2 positive, or a good response is seen early in treatment.

Choice of chemotherapy schedule is dependant on receptor profile, stage and patient fitness. For an algorithm for choice of treatment see the guidelines section below. In summary;

  • ER+: (F)EC-T x6 or if high risk/young consider accelerated EC-weekly paclitaxel
  • HER2+: (F)EC-Trastuzumab+Pertuzumab x7
  • Triple negative: (F)EC-T(C) x6 or if high risk/young consider accelerated EC- weekly paclitaxel+/-carboplatin esp if BRCA+

(F) as many centres are now choosing to drop the 5FU as increasing data to suggest there is no additional benefit for its addition but it can add toxicity.

Adjuvant

The overview of randomised trials of polychemotherapy for early breast cancer shows an absolute 10-year survival benefit in women under 50 years old with node positive disease of around 11% and node negative disease 7%. The absolute survival benefit falls with age but statistically significant survival benefit is still seen up to but not beyond the age of 70.

A survival benefit for chemotherapy over and above that achieved with endocrine therapy alone is seen in patients whose tumours are ER positive.

The decision to offer chemotherapy is based on many factors including age, general clinical condition, prognostic factors for outcome and the patient’s own wishes following informed discussion. Predictive tools such as ‘Adjuvant on line’ and ‘PREDICT’ may be useful.

Low risk

In this category, the absolute survival benefit for adjuvant chemotherapy is either unproven or so small as to be not clinically recommended.

  • Patients aged 70 or over: chemotherapy may need to be discussed with some patients aged over 70 with multiple poor risk factors but deemed fit for chemotherapy. This is always an MDT/consultant decision.

Patients with all of the following:

  • – tumour ≤2cm in diameter
  • – ER positive
  • – Grade 1 histology
  • – no lympho-vascular invasion
  • – negative lymph nodes
  • – HER2 negative.

Moderate to high risk

Patients with any of the following are at sufficient risk to offer adjuvant chemotherapy on the basis of established survival benefits. For each patient, the pros and cons of the treatment need to be discussed. As a general guideline, the greater the number of factors involved, the greater the risk and the stronger the recommendation for chemotherapy:

  • node positive disease
  • ER negative - if triple negative should see to discuss chemotherapy even in T1N0 disease
  • lympho-vascular invasion present
  • Grade 2 and 3 histology
  • tumour ≥2cm in diameter
  • patients ≤35 years
  • HER2 positive - any >1cm should be seen to discuss adjuvant chemotherapy+anti-HER2 treatment.

Use of genomic signatures

In patients with node negative ER+/HER2- tumours with intermediate risk for chemotherapy ONCOTYPE Dx is used to help further identify patients at low risk of recurrence where the benefits of chemotherapy are negligible and patients can safely be spared chemotherapy.

Intermediate prognosis can be estimated using the Nottingham Prognostic index (NPI) or predict/adjuvant online tools where benefit is estimated to be approx 3-5%.

Within the MINDACT clinical trial low risk was; G1<3cm, G2 <2cm and G3<1cm and high clinical risk was G1>3cm, G2>2cm and G3>1cm and in these high risk patients the mammaprint gene signature test was used and if high clinical risk but low genomic risk the 5 year survival was only 1.5% higher with chemotherapy.

For choice of chemotherapy regimens see algorithms in guidelines section but in summary;

  • In ER+: (F)EC-T x6
  • In HER2+: (F)EC-Trastuzumab+Pertuzumab(if node positive) x6 with antiher2 continued for 1 year
  • In triple negative: (F)EC-T x6 or consider in high risk/young accelerated EC-weekly paclitaxel

Other regimes to consider for older/less fit patients or if anthracyclines contraindicated

  • In ER+: docetaxel/cyclophosphamide (TC)x4
  • In HER2+: docetaxel/carboplatin (TC) x6 + H+/-P(if node positive) for a year or another option if less fir or in <2cm N0 weekly paclitaxel x12 with herceptin for 6-12 months

Metastatic

The choice of chemotherapy will depend on receptor status, disease factors (eg, CNS disease), patient fitness and previous treatment.

It is not possible, therefore, to recommend which regimen should be used in which circumstance (except to note the NICE guidance).
The following regimens are all acceptable and for suggested algorithm see guidelines section below. In summary;

  • Anthracyline naïve or retreatment
    Note: maximum allowable dose for doxorubicin is 450–550mg/m2 and for epirubicin 950mg/m2, although less if other cardiac risk factors are present or prior mediastinal radiotherapy
    Single agent epirubicin – 3-weekly Dose usually 60–90mg/m2 IV day 1
    Single agent epirubicin – weekly Dose usually 20–30mg/m2 IV day 1
    EC (epirubicin and cyclophosphamide) -Dose usually 60–90mg/m2 and 600mg/m2 respectively IV day 1 3-weekly.
  • Docetaxel and paclitaxel are recommended as an option for the treatment of advanced breast cancer where initial chemotherapy (including an anthracycline) has failed or is inappropriate or Abraxane (albumin-bound paclitaxel) is an alternative treatment for breast cancer in patients who have documented taxane hypersensitivity.

Other chemotherapy agents for advanced disease:

  • Capecitabine 1250mg/m2 PO BD on days 1–14 every 21 days is the licenced starting dose; however, consider commencing at 1000mg/m2 for frailer patients.
  • Eribulin 1.23mg/m2 (1.4mg/m2 eribulin mesylate) IV over 2–5 minutes day 1 and day 8 every 21 days until disease progression (Available through the national Cancer Drugs Fund as third line option)
  • Vinorelbine intravenous therapy 25–30mg/m2 weekly (or day 1 and day 8 every 21 days if being used in combination schedules) or Vinorelbine oral therapy 60mg/m2 weekly for the first three administrations and then beyond the third administration, it is recommended to increase the dose to 80mg/m2 once weekly except in those patients for whom the neutrophil count dropped once below 500/mm3 or more than once between 500 and 1000/mm3 during the first three administrations at 60mg/m2.
  • Gemcitabine and carboplatin - Gemcitabine 1000mg/m2 day 1 and day 8
    Carboplatin AUC 5 day 1 every 21 days. Especially for patients with triple negative breast cancer.

In HER2 positive disease first line is docetaxel + herceptin/pertuzumab x6 with HP continued until progression. Second line is Kadcyla then as above for further lines +/- hercepin which should continue if only CNS progression.

In triple negative disease in patients who are PDL1+ (>1%) the first line is atezolizumab with nab-paclitaxel.


Teaching session on metastatic breast cancer treatment, Dr Comins, 2020

Endocrine therapy

In patients with hormone receptor positive disease.

Adjuvant

Pre-menopausal

  • Tamoxifen for 10 years in pre-menopausal women

Consider the addition of ovarian suppression with LHRHa injections for 5 years (this can be given either with tamoxifen or an aromatase inhibitor) as adjuvant ovarian ablation reduces the risk of breast cancer recurrence in pre-menopausal patients as demonstrated by SOFT/TEXT trial.

Post-menopausal

  • Aromatase inhibitors for 5-10 years in post-menopausal women (10 years reduces breast cancer risk but not overall survival, can be offered to women at highest risk of relapse - often those with node positive disease)

Metastatic

If not in visceral crisis then the use of an AI +/- LHRHa (if premenopausal)

Now several CDK4/6 inhibitors (palbociclib, abemaciclib, ribociclib) in use and if patient performance status/co-morbidities allow would add this in to improve PFS and some studies also demonstrate OS benefit.

  • If already on tamoxifen at time when develops metastatic disease then as above, if on an AI (or stopped within 12 months of diagnosis) then can use CDK4/6 with fulvestrant.
  • If only treated with tamoxifen/AI in the first line setting can then use CDK4/6 with fulvestrant in second line

If good response to first/second line endocrine treatment and no impending visceral crisis then can consider exemestane+everlimus. Evidence for this was before the use of CDK4/6 so data for its response in this setting is not clear.

On development of hormone resistance/visceral disease progression then move onto chemotherapy options.

Joint SOFT+TEXT analysis
SOFT+TEXT
Ovarian suppression in pre menopausal

ATLAS trial
ATLAS
10 years of tamoxifen

MA17 trial
MA17
10 years of aromatase inhibitors

Improving Adjuvant Endocrine Treatment Tailoring in Premenopausal Women With Hormone Receptor–Positive Breast Cancer
Lambertini et al
JCO 2020

Improving Adjuvant Endocrine Treatment Tailoring in Premenopausal Women With Hormone Receptor–Positive Breast Cancer

Supportive treatments

Use of bisphosphonates in the adjuvant setting has demonstrated improved outcomes for post menopausal women with early breast cancer. Benefit is mostly in those at highest risk of relapse therefore should be offered to post menopausal women who were at high enough risk to have had chemo.

Use of bisphosphonates/denosumab in the metastatic setting can help reduce bone disease related events.

Adj bisphosphonate meta-analysis
EBCTCG
Adj bisphosphonate meta-analysis

Guidelines and other documents

chemotherapy algorithm for treatment of early breast cancer
st lukes cancer centre
chemotherapy algorithm for treatment of early breast cancer

algorithm for treatment of metastatic disease
St Lukes cancer centre
algorithm for treatment of metastatic disease

London cancer alliance guidelines
LCA, last updated 2016
LCA

NICE breast cancer guidelines 2018
NICE
NICE