Recommendations

People have the right to be involved in discussions and make informed decisions about their care, as described in NICE's information on making decisions about your care.

Breast cancer affects women and men, and can affect those who have undergone a gender reassignment or who are non‑binary. We have used the term 'women' in this guideline for recommendations that usually only relate to women (such as breast‑conserving surgery) and 'people' in all other cases. However, no discrimination is intended and recommendations relate to all those who have early or locally advanced breast cancer.

Making decisions using NICE guidelines explains how we use words to show the strength (or certainty) of our recommendations, and has information about prescribing medicines (including off‑label use), professional guidelines, standards and laws (including on consent and mental capacity), and safeguarding.

1.1 Referral, diagnosis and preoperative assessment

Preoperative assessment of the breast and axilla

1.1.1 Do not routinely use MRI of the breast in the preoperative assessment of people with biopsy‑proven invasive breast cancer or ductal carcinoma in situ (DCIS). [2009]

1.1.2 Offer MRI of the breast to people with invasive breast cancer:

  • if there is discrepancy regarding the extent of disease from clinical examination, mammography and ultrasound assessment for planning treatment

  • if breast density precludes accurate mammographic assessment

  • to assess the tumour size if breast‑conserving surgery is being considered for invasive lobular cancer. [2009]

Preoperative staging of the axilla

1.1.3 Perform pretreatment ultrasound evaluation of the axilla for people having investigations for early invasive breast cancer and, if abnormal lymph nodes are identified, perform ultrasound‑guided needle sampling. [2009]

Genetic testing

1.1.4 Offer genetic testing for BRCA1 and BRCA2 mutations to women under 50 years with triple‑negative breast cancer, including those with no family history of breast or ovarian cancer. (Also see the recommendations on genetic testing in the NICE guideline on familial breast cancer.) [2017, amended 2018]

1.2 Providing information and psychological support

1.2.1 All members of the breast cancer clinical team should follow the recommendations on communication in NICE's guideline on patient experience in adult NHS services. [2009, amended 2018]

1.2.2 All people with breast cancer should have a named clinical nurse specialist or other specialist key worker with equivalent skills, who will support them throughout diagnosis, treatment and follow‑up. [2009, amended 2018]

1.2.3 Offer all people with breast cancer prompt access to specialist psychological support and, where appropriate, psychiatric services. [2009]

1.2.4 Discuss opportunities for people with breast cancer to be involved in research, and encourage entry into clinical trials and other studies. [2018]

1.2.5 For guidance on fertility preservation, see the recommendations on people with cancer who wish to preserve fertility in the NICE guideline on fertility problems. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on providing information and psychological support.

1.3 Surgery to the breast

1.3.1 Offer further surgery (re‑excision or mastectomy, as appropriate) after breast‑conserving surgery where invasive cancer and/or DCIS is present at the radial margins ('tumour on ink'; 0 mm). [2018]

1.3.2 For women who have had breast‑conserving surgery where invasive cancer and/or DCIS is present within 2 mm of, but not at, the radial margins (greater than 0 mm and less than 2 mm):

  • discuss the benefits and risks of further surgery (re‑excision or mastectomy) to minimise the risk of local recurrence

  • take into account the woman's preferences, comorbidities, tumour characteristics and the potential use of radiotherapy (also see radiotherapy after breast‑conserving surgery). [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on surgery to the breast.

Full details of the evidence and the committee's discussion are in evidence review A: surgery to the breast.

1.3.3 All breast units should audit their recurrence rates after treatment. [2009, amended 2018]

Paget's disease

1.3.4 Offer breast‑conserving surgery with removal of the nipple–areolar complex as an alternative to mastectomy for people with Paget's disease of the nipple that has been assessed as localised. Offer oncoplastic repair techniques to maximise cosmesis. [2009]

1.4 Surgery to the axilla

Invasive breast cancer

1.4.1 Perform minimal surgery, rather than lymph node clearance, to stage the axilla for people with invasive breast cancer and no evidence of lymph node involvement on ultrasound or a negative ultrasound‑guided needle biopsy. Sentinel lymph node biopsy (SLNB) is the preferred technique. [2009]

1.4.2 Perform SLNB using the dual technique with isotope and blue dye. [2009]

1.4.3 Breast units should audit their axillary recurrence rates. [2009]

Ductal carcinoma in situ

1.4.4 Do not perform SLNB routinely for women with a preoperative diagnosis of DCIS who are having breast‑conserving surgery, unless they are considered to be at high risk of invasive disease. People at high risk of invasive disease include those with a palpable mass or extensive microcalcifications. Risk can be estimated using a range of standardised tools and clinical expertise. [2009]

1.4.5 Offer SLNB to all people who are having a mastectomy for DCIS. [2009]

Evaluation and management of a positive axillary lymph node identified by a preoperative ultrasound‑guided needle biopsy

1.4.6 Offer axillary node clearance to people with invasive breast cancer who have a preoperative ultrasound‑guided needle biopsy with pathologically proven lymph node metastases. [2009, amended 2018]

Evaluation and management of a positive axillary lymph node identified by a sentinel lymph node biopsy (in people with a normal preoperative ultrasound‑guided needle biopsy)

1.4.7 Offer further axillary treatment (axillary node clearance or radiotherapy) after SLNB to people who have 1 or more sentinel lymph node macrometastases. [2018]

1.4.8 Discuss the benefits and risks of having no further axillary treatment after primary breast‑conserving surgery (within clinical trials where available) with women who:

  • have 1 or 2 sentinel lymph node macrometastases and

  • have been advised to have whole‑breast radiotherapy with systemic therapy (which may be endocrine therapy). [2018]

1.4.9 Do not offer further axillary treatment after primary surgery to people with invasive breast cancer who have only micrometastases in their sentinel lymph nodes. [2018]

1.4.10 Do not offer further axillary treatment after primary surgery to people with invasive breast cancer who have only isolated tumour cells in their sentinel lymph nodes. Regard these people as having lymph node‑negative breast cancer. [2018]

For a short explanation of why the committee made the 2018 recommendations, and how they might affect practice, see the rationale and impact section on evaluation and management of a positive axillary lymph node.

Full details of the evidence and the committee's discussion are in evidence review B: management of the positive axilla.

1.5 Breast reconstruction

1.5.1 Offer both breast reconstruction options to women (immediate reconstruction and delayed reconstruction), whether or not they are available locally. [2018]

1.5.2 Be aware that some women may prefer not to have breast reconstruction surgery. [2018]

1.5.3 Offer immediate breast reconstruction to women who have been advised to have a mastectomy, including those who may need radiotherapy, unless they have significant comorbidities that rule out reconstructive surgery. [2018]

1.5.4 Discuss the benefits and risks of immediate breast reconstruction and delayed breast reconstruction with women. Topics to discuss include those in table 1 and:

  • the timing of breast reconstruction surgery (at the same time as mastectomy or later)

  • different breast reconstruction surgery options and what they involve

  • how the timing of breast reconstruction surgery affects the options available

  • the uncertainty over long‑term outcomes in women having radiotherapy. [2018]

Table 1 Breast reconstruction options for women who choose breast reconstruction

-

Immediate breast reconstruction

Delayed breast reconstruction

Definition

Reconstruction is started in the same operation as the mastectomy

After a mastectomy, reconstruction is done in a separate operation

Number and timing of operations

More than 1 operation is usually needed to complete the reconstruction

The total number of operations will vary. It may be affected by factors such as:

  • type of reconstruction (for example, some are planned in stages; a prosthesis may be worn until reconstruction is complete)

  • personal preferences (such as whether a nipple reconstruction is requested)

Fewer operations may be needed

More than 1 operation is usually needed to complete the reconstruction

The total number of operations will vary. It may be affected by factors such as:

  • type of reconstruction (for example, some are planned in stages; a prosthesis may be worn until reconstruction is complete)

  • personal preferences (such as whether a nipple reconstruction is requested)

More operations may be needed

Breast reconstruction options available

These will vary depending on personal preferences (such as breast size desired), current body shape, other health conditions, previous operations and lifestyle factors (such as hobbies)

Not all hospitals or surgeons can offer all procedures. Travel to a different hospital may be needed for a specific option

Options may be available that spare or preserve the breast skin (which may mean less scarring and a more natural look)

Limited time to make a decision about options (which may include not having a reconstruction) before surgery

These will vary depending on personal preferences (such as breast size desired), current body shape, other health conditions, previous operations and lifestyle factors (such as hobbies)

Not all hospitals or surgeons can offer all procedures. Travel to a different hospital may be needed for a specific option

Certain options that spare or preserve the breast skin may not be available

More time to make a decision (which may include not having a reconstruction) and to plan reconstruction

Benefits

Breast shape remains, which may have psychological benefits

Lifestyle changes (such as losing weight and taking regular exercise) may be possible, which increase the options and lower the risks of reconstruction surgery

Procedures (and associated recovery) can be planned around other commitments

Risks

Surgical complications can occur after any breast reconstruction and will vary by type of procedure and personal risk factors

May be lower rates of:

  • tissue breakdown

  • surgery for flap removal if it cannot be used because of a complication (which may lead to delayed reconstruction and flat appearance for a period of time)

  • procedures to improve symmetry

Complications from the mastectomy or axillary surgery can occur during the recovery period

Surgical complications can occur after any breast reconstruction and will vary by type of procedure and personal risk factors

May be lower rates of:

  • mastectomy site complications

  • flap or implant failure (which may lead to delayed reconstruction and flat appearance for a period of time)

  • capsular contracture (a scar layer around the implant that may lead to pain if severe)

May need to interrupt hormone therapies (tamoxifen) for further surgery

Satisfaction

No clear differences in satisfaction with completed reconstructions

No clear differences in satisfaction with completed reconstructions

Reconstruction and adjuvant therapy (including radiotherapy and chemotherapy)

Radiotherapy or chemotherapy can be given but may be delayed if there are complications from the mastectomy or reconstruction

Immediate reconstructions using implants may be more affected by radiotherapy than immediate flap reconstructions

May need adaptions to scans if a tissue expander is used. For example, may not be able to have MRI scans and may need modified radiotherapy planning

Complications can also occur after mastectomy alone, which may delay chemotherapy or radiotherapy

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on breast reconstruction.

Full details of the evidence and the committee's discussion are in evidence review I: postmastectomy radiotherapy.

1.6 Diagnostic assessment and adjuvant therapy planning

Predictive factors

1.6.1 Request the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2) status of all invasive breast cancers simultaneously at the time of initial histopathological diagnosis. [2018]

1.6.2 Assess the ER status of all invasive breast cancers using standardised and quality‑assured immunohistochemical techniques, and report the results quantitatively. [2009]

1.6.3 Assess the PR status of all invasive breast cancers using standardised and quality‑assured immunohistochemical techniques, and report the results quantitatively. [2018]

1.6.4 Assess the HER2 status of all invasive breast cancers using standardised and quality‑assured techniques, and report the results quantitatively. [2009]

1.6.5 Ensure that the ER, PR and HER2 statuses are available and recorded at the preoperative and postoperative multidisciplinary team meetings when systemic treatment is discussed. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on predictive factors.

Full details of the evidence and the committee's discussion are in evidence review C: adjuvant systemic therapy planning.

Adjuvant therapy planning

1.6.6 Consider adjuvant therapy after surgery for people with invasive breast cancer, and ensure that recommendations are recorded at the multidisciplinary team meeting. [2009]

1.6.7 Base recommendations about adjuvant therapy on multidisciplinary team assessment of the prognostic and predictive factors, and the possible risks and benefits of the treatment. Make decisions with the person after discussing these factors. [2009, amended 2018]

1.6.8 Use the PREDICT tool to estimate prognosis and the absolute benefits of adjuvant therapy for women with invasive breast cancer. [2018]

1.6.9 When using version 2.0 of the PREDICT tool, be aware that:

  • it is less accurate for:

    • women under 30 with ER‑positive breast cancer

    • women aged 70 and over

    • women with tumours larger than 50 mm

  • it has not been validated in men and

  • the validation may have under‑represented some ethnic groups.

    Note the potential limitations in versions of PREDICT after 2.0 may differ from those listed here. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on adjuvant therapy planning.

Full details of the evidence and the committee's discussion are in evidence review C: adjuvant systemic therapy planning.

Tumour profiling tests to guide adjuvant chemotherapy decisions

The NICE guidance on tumour profiling tests provides evidence-based recommendations on tumour profiling tests to guide adjuvant chemotherapy decisions.

1.7 Endocrine therapy

1.7.1 Treat people with invasive breast cancer, irrespective of age, with surgery and appropriate systemic therapy, rather than endocrine therapy alone, unless significant comorbidity precludes surgery. [2009]

Adjuvant endocrine therapy for invasive breast cancer

1.7.2 Offer tamoxifen as the initial adjuvant endocrine therapy for men and premenopausal women with ER‑positive invasive breast cancer. [2009, amended 2018]

1.7.3 Offer an aromatase inhibitor as the initial adjuvant endocrine therapy for postmenopausal women with ER‑positive invasive breast cancer who are at medium or high risk of disease recurrence. Offer tamoxifen to women who are at low risk of disease recurrence, or if aromatase inhibitors are not tolerated or are contraindicated. Risk can be estimated using a range of standardised tools and clinical expertise. (Please refer to the summary of product characteristics for individual aromatase inhibitors because there are differences in their licensed indications.) [2009, amended 2018]

Ovarian function suppression

1.7.4 Consider ovarian function suppression in addition to endocrine therapy for premenopausal women with ER‑positive invasive breast cancer. [2018]

1.7.5 Discuss the benefits and risks of ovarian function suppression in addition to endocrine therapy with premenopausal women with ER‑positive invasive breast cancer. Explain to women that ovarian function suppression may be most beneficial for those women who are at sufficient risk of disease recurrence to have been offered chemotherapy. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on ovarian function suppression.

Full details of the evidence and the committee's discussion are in evidence review D: endocrine therapy for invasive disease.

Extended endocrine therapy

In July 2018, the use of aromatase inhibitors in recommendations 1.7.6 and 1.7.7 was off label. See NICE's information on prescribing medicines. Please refer to the summary of product characteristics for individual aromatase inhibitors because there are differences in their licensed indications.

1.7.6 Offer extended therapy (total duration of endocrine therapy of more than 5 years) with an aromatase inhibitor for postmenopausal women with ER‑positive invasive breast cancer who are at medium or high risk of disease recurrence and who have been taking tamoxifen for 2 to 5 years. Medium or high risk may include people who have lymph node‑positive breast cancer, with tumours that are T2 or greater and higher grade. [2018]

1.7.7 Consider extended therapy (total duration of endocrine therapy of more than 5 years) with an aromatase inhibitor for postmenopausal women with ER‑positive invasive breast cancer who are at low risk of disease recurrence and who have been taking tamoxifen for 2 to 5 years.
Low risk may include people with lymph node‑negative breast cancer, with smaller or lower‑grade tumours. [2018]

1.7.8 Consider extending the duration of tamoxifen therapy for longer than 5 years for both premenopausal and postmenopausal women with ER‑positive invasive breast cancer. [2018]

1.7.9 Discuss the benefits and risks of extended endocrine therapy with women. Topics to discuss include those in table 2. [2018]

Table 2 Effects of extended endocrine therapy

-

Extended tamoxifen therapy (after an initial 5 years of tamoxifen therapy)

Extended endocrine therapy with an aromatase inhibitor (after 5 years of tamoxifen therapy)

Definition

Continuing to take tamoxifen after 5 years of tamoxifen therapy

Switching to an aromatase inhibitor after 5 years of tamoxifen therapy

Who can take this therapy

Premenopausal or postmenopausal women with ER‑positive invasive breast cancer

Postmenopausal women with ER‑positive invasive breast cancer

Effect on breast cancer recurrence

NOTE: The benefit for an individual person will depend on the risk of their cancer returning. For people with a low risk of recurrence, the benefits may not outweigh the risks or side effects

Medium or high risk may include people who have lymph node‑positive breast cancer, with tumours that are T2 or greater and higher grade. Low risk may include people with lymph node‑negative breast cancer, with smaller or lower‑grade tumours

Lower rates of breast cancer recurrence compared with 5 years of tamoxifen therapy

Lower rates of breast cancer recurrence compared with 5 years of tamoxifen therapy

In postmenopausal women, switching to an aromatase inhibitor may be more effective at reducing recurrence than continuing with tamoxifen

Side effects

NOTE: These are common side effects experienced during additional years taking endocrine therapy. Most effects are reversible when tablets are stopped

Side effects of endocrine therapy will continue for additional years (for example, menopausal symptoms such as hot flushes)

With extended use of tamoxifen: increased risk of thrombosis and endometrial cancer, and possibly bone density loss in premenopausal women

Side effects of endocrine therapy will continue for additional years (for example, menopausal symptoms such as hot flushes)

With extended use of aromatase inhibitors: bone density loss, and joint and muscle pain

Fertility and family planning

Effects on fertility and family planning will continue for additional years as women should not become pregnant while taking tamoxifen, or within 2 months of stopping, because it may have adverse effects on the baby

Not applicable as postmenopausal women only

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on extended endocrine therapy.

Full details of the evidence and the committee's discussion are in evidence review D: endocrine therapy for invasive disease.

Endocrine therapy for ductal carcinoma in situ

1.7.10 Offer endocrine therapy after breast‑conserving surgery for women with ER‑positive DCIS if radiotherapy is recommended but not received. [2018]

1.7.11 Consider endocrine therapy after breast‑conserving surgery for women with ER‑positive DCIS if radiotherapy is not recommended. [2018]

1.7.12 Discuss the benefits and risks of endocrine therapy after breast‑conserving surgery for women with ER‑positive DCIS. Topics to discuss include those in table 3. [2018]

Table 3 Effects of endocrine therapy after breast‑conserving surgery for women with ER‑positive DCIS

-

Endocrine therapy after breast‑conserving surgery for women with ER‑positive DCIS

Definition

Tamoxifen or an aromatase inhibitor for 5 years. Taken as a once‑daily tablet

Effect on survival and disease recurrence

NOTE: The benefit for an individual person will depend on the risk of their cancer returning. For people with low risk of recurrence, the benefits may not outweigh the risks or side effects.

Risk can be estimated using a range of standardised tools and clinical expertise

No effect on how many women are alive 5 and 10 years after diagnosis

Lower rate of recurrence of DCIS and lower rate of invasive breast cancer, compared with women who did not receive endocrine therapy or radiotherapy after surgery

Side effects

All endocrine therapies: menopausal symptoms such as hot flushes

For tamoxifen: increased risk of thrombosis, endometrial cancer and possibly bone density loss in premenopausal women

For aromatase inhibitors: joint and muscle pain, urogenital symptoms and bone density loss

Fertility and family planning

Effects on fertility and family planning as women should not become pregnant while taking tamoxifen, or within 2 months of stopping, because it may have adverse effects on the baby

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on endocrine therapy for DCIS.

Full details of the evidence and the committee's discussion are in evidence review D: endocrine therapy for invasive disease.

1.8 Adjuvant chemotherapy for invasive breast cancer

1.8.1 For people with breast cancer of sufficient risk that chemotherapy is indicated, offer a regimen that contains both a taxane and an anthracycline. Please refer to the summaries of product characteristics for individual taxanes and anthracyclines because there are differences in their licensed indications. [2018]

1.8.2 Discuss with people the benefits and risks of adding a taxane to anthracycline‑containing regimens. Topics to discuss include those in table 4 and:

  • the benefits of reduced cardiac toxicity and reduced nausea

  • the risks of additional side effects, including neuropathy, neutropenia and hypersensitivity

  • the different side effects and dosing frequencies of different docetaxel and paclitaxel regimens, and the additional clinic visits that may be needed

  • that absolute benefit is proportional to absolute risk of recurrence.

    Please refer to the summaries of product characteristics for individual taxanes and anthracyclines because there are differences in their licensed indications. [2018]

Table 4 Benefits and risks of adding a taxane to anthracycline‑containing regimens and comparison of different taxane regimens

Effect of adding a taxane to an anthracycline containing regimen

3‑weekly docetaxel

Weekly or fortnightly paclitaxel

Effect on survival

NOTE: The benefit for an individual person will depend on the risk of their cancer returning. For people with low risk of recurrence, the benefits may not outweigh the risks or side effects

Risk can be estimated using a range of standardised tools and clinical expertise

Some evidence for improved outcomes including reducing the risk of breast cancer returning and increasing the chance of surviving

Some evidence for improved outcomes including reducing the risk of breast cancer returning and increasing the chance of surviving

Benefits

Smaller doses of anthracyclines can be used, which can reduce the risk of side effects such as nausea and vomiting

Smaller cumulative doses of individual drugs may reduce long‑term side effects, for example, cardiac toxicity and risk of second malignancies

Smaller doses of anthracyclines can be used, which can reduce the risk of side effects such as nausea and vomiting

Smaller cumulative doses of individual drugs may reduce long‑term side effects, for example, cardiac toxicity and risk of second malignancies

Side effects

Additional side effects may include joint and muscle pain, nerve damage, higher rates of febrile neutropenia and hypersensitivity reactions

Some people have long‑term hair loss (alopecia) after treatment with taxanes

Additional side effects may include nerve damage and hypersensitivity reactions but febrile neutropenia is less likely than with 3‑weekly docetaxel

Some people have long‑term hair loss (alopecia) after treatment with taxanes

Weekly paclitaxel is tolerated best, but even fortnightly is better tolerated than 3‑weekly docetaxel

Administration

Visits to hospital every 3 weeks

Visits to hospital every week or every 2 weeks

Length of course

9 to 12 weeks (3 to 4 cycles)

9 to 12 weeks (9 to 12 doses)

1.8.3 Weekly and fortnightly paclitaxel should be available locally because these regimens are tolerated better than 3‑weekly docetaxel, particularly in people with comorbidities. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on adjuvant chemotherapy for invasive breast cancer.

Full details of the evidence and the committee's discussion are in evidence review E: adjuvant chemotherapy.

Biological therapy

1.8.4 Offer adjuvant trastuzumab for people with T1c and above HER2‑positive invasive breast cancer, given at 3‑week intervals for 1 year in combination with surgery, chemotherapy and radiotherapy as appropriate. [2009, amended 2018]

1.8.5 Consider adjuvant trastuzumab for people with T1a/T1b HER2‑positive invasive breast cancer, taking into account any comorbidities, prognostic features and possible toxicity of chemotherapy. [2018]

For a short explanation of why the committee made the 2018 recommendation and how it might affect practice, see the rationale and impact section on biological therapy.

Full details of the evidence and the committee's discussion are in evidence review F: adjuvant biological therapy.

1.8.6 Assess cardiac function before starting treatment with trastuzumab. [2009]

1.8.7 Use trastuzumab with caution in people with HER2‑positive invasive breast cancer who have any of the following:

  • a baseline left ventricular ejection fraction (LVEF) of 55% or less

  • a history of, or current, congestive heart failure

  • a history of myocardial infarction

  • angina pectoris needing medication

  • cardiomyopathy

  • cardiac arrhythmias needing medical treatment

  • clinically significant valvular heart disease

  • haemodynamic effective pericardial effusion

  • poorly controlled hypertension. [2009, amended 2018]

1.8.8 Repeat cardiac function assessments every 3 months during trastuzumab treatment. If the LVEF drops by 10 percentage (ejection) points or more from baseline and to below 50%, suspend trastuzumab treatment. Restart trastuzumab only after reassessing cardiac function and discussing the possible benefits and risks. Cardiac function assessments should also be repeated every 6 months following discontinuation of treatment until 24 months from the last administration of trastuzumab. [2009, amended 2018]

1.9 Bisphosphonate therapy

Adjuvant bisphosphonate therapy

In July 2018, the use of bisphosphonates (zoledronic acid or sodium clodronate) in recommendations 1.9.1 and 1.9.2 was off label. See NICE's information on prescribing medicines.

1.9.1 Offer bisphosphonates (zoledronic acid or sodium clodronate) as adjuvant therapy to postmenopausal women with node‑positive invasive breast cancer. [2018]

1.9.2 Consider bisphosphonates (zoledronic acid or sodium clodronate) as adjuvant therapy for postmenopausal women with node‑negative invasive breast cancer and a high risk of recurrence. Risk can be estimated using a range of standardised tools and clinical expertise. [2018]

1.9.3 Discuss the benefits and risks of bisphosphonate treatment with women, particularly the risk of osteonecrosis of the jaw, atypical femoral fractures and osteonecrosis of the external auditory canal. Follow the Medicines and Healthcare products Regulatory Agency/Commission on Human Medicines (MHRA/CHM) advice on bisphosphonates. [2018]

To find out why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on adjuvant bisphosphonate therapy.

Full details of the evidence and the committee's discussion are in evidence review G: adjuvant bisphosphonates.

Bone health

1.9.4 Offer a baseline dual‑energy X‑ray absorptiometry (DEXA) scan to assess bone mineral density (BMD) in women with invasive breast cancer who are not receiving bisphosphonates as adjuvant therapy and who:

  • are starting adjuvant aromatase inhibitor treatment or

  • have treatment‑induced menopause or

  • are starting ovarian ablation/suppression therapy. [2009, amended 2018]

1.9.5 Do not offer a DEXA scan to women with invasive breast cancer who are receiving tamoxifen alone, regardless of their pretreatment menopausal status. [2009]

1.9.6 Offer bisphosphonates to women identified by algorithms 1 and 2 in Guidance for the management of breast cancer treatment‑induced bone loss: a consensus position statement from a UK expert group (2008; this guidance is not NICE accredited). [2009]

1.10 Radiotherapy

1.10.1 Use a radiotherapy technique that minimises the dose to the lung and heart. [2018]

1.10.2 Use a deep inspiratory breath‑hold radiotherapy technique for people with left‑sided breast cancer to reduce the dose to the heart. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on radiotherapy techniques.

Full details of the evidence and the committee's discussion are in evidence review H: breast radiotherapy.

Radiotherapy after breast‑conserving surgery

1.10.3 Offer whole‑breast radiotherapy to women with invasive breast cancer who have had breast‑conserving surgery with clear margins. [2018]

1.10.4 Consider partial breast radiotherapy (as an alternative to whole‑breast radiotherapy) for women who have had breast‑conserving surgery for invasive cancer (excluding lobular type) with clear margins and who:

  • have a low absolute risk of local recurrence (defined as women aged 50 and over with tumours that are 3 cm or less, N0, ER‑positive, HER2‑negative and grade 1 to 2) and

  • have been advised to have adjuvant endocrine therapy for a minimum of 5 years. [2018]

1.10.5 When considering partial breast radiotherapy (see recommendation 1.10.4), discuss the benefits and risks, and explain that:

  • local recurrence with partial breast radiotherapy at 5 years is equivalent to that with whole‑breast radiotherapy

  • the risk of local recurrence beyond 5 years is not yet known

  • there is a potential reduction in late adverse effects. [2018]

1.10.6 When delivering partial breast radiotherapy, use external beam radiotherapy. [2018]

1.10.7 Consider omitting radiotherapy for women who:

  • have had breast‑conserving surgery for invasive breast cancer with clear margins and

  • have a very low absolute risk of local recurrence (defined as women aged 65 and over with tumours that are T1N0, ER‑positive, HER2‑negative and grade 1 to 2) and

  • are willing to take adjuvant endocrine therapy for a minimum of 5 years. [2018]

1.10.8 When considering omitting radiotherapy for the population in recommendation 1.10.7, discuss the benefits and risks, including those in table 5, and explain that:

  • without radiotherapy, local recurrence occurs in about 50 women per 1,000 at 5 years, and with radiotherapy, occurs in about 10 women per 1,000 at 5 years

  • overall survival at 10 years is the same with or without radiotherapy

  • there is no increase in serious late effects if radiotherapy is given (for example, congestive cardiac failure, myocardial infarction or secondary cancer). [2018]

Table 5 Benefits and risks of radiotherapy compared with no radiotherapy in the group of women at low risk described in recommendation 1.10.7

-

Radiotherapy

No radiotherapy

Effect on local recurrence

On average, in 1,000 women, over 5 years local recurrence occurs in about 10 women, and does not occur in about 990 women

On average, in 1,000 women, over 5 years local recurrence occurs in about 50 women, and does not occur in about 950 women

Effect on survival

No difference in overall survival at 10 years

No difference in overall survival at 10 years

Risks

Possibility of short‑ and long‑term adverse effects on the breast, and resulting cosmetic changes (such as skin soreness, changes to colour of skin, radiation fibrosis or stiffening of the breast tissue)

No short‑ or long‑term adverse effects on the breast, or cosmetic changes

Side effects

In this group of women at low risk, there is no increase in serious late side effects of radiotherapy (such as congestive cardiac failure, myocardial infarction or secondary cancer)

No side effects of radiotherapy will occur

Administration

Given at the treatment centre 5 days a week for 3 weeks after surgery

No need to attend the treatment centre for radiotherapy sessions

1.10.9 Consider adjuvant radiotherapy for women with DCIS following breast‑conserving surgery with clear margins, and discuss with them the possible benefits and risks of radiotherapy (also see the section on surgery to the breast). [2009, amended 2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on radiotherapy after breast‑conserving surgery.

Full details of the evidence and the committee's discussion are in evidence review H: breast radiotherapy.

Radiotherapy after mastectomy

1.10.10 Offer adjuvant postmastectomy radiotherapy to people with node‑positive (macrometastases) invasive breast cancer or involved resection margins. [2018]

1.10.11 Consider adjuvant postmastectomy radiotherapy for people with node‑negative T3 or T4 invasive breast cancer. [2018]

1.10.12 Do not offer radiotherapy following mastectomy to people with invasive breast cancer who are at low risk of local recurrence (for example, most people who have lymph node‑negative breast cancer). Risk can be estimated using a range of standardised tools and clinical expertise. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on radiotherapy after mastectomy.

Full details of the evidence and the committee's discussion are in evidence review I: postmastectomy radiotherapy.

Dose fractionation

1.10.13 Use external beam radiotherapy giving 40 Gy in 15 fractions as standard practice for women with invasive breast cancer after breast‑conserving surgery or mastectomy. [2009]

Breast boost following breast‑conserving surgery

1.10.14 Offer an external beam boost to the tumour bed for women with invasive breast cancer and a high risk of local recurrence, following whole‑breast radiotherapy. Risk can be estimated using a range of standardised tools and clinical expertise. [2009, amended 2018]

1.10.15 Inform women of the risk of side effects associated with an external beam boost to the tumour bed following whole‑breast radiotherapy. [2009, amended 2018]

Radiotherapy to nodal areas

1.10.16 Do not offer adjuvant radiotherapy to regional lymph nodes to people with invasive breast cancer who have been shown to have histologically lymph node‑negative breast cancer. [2009, amended 2018]

1.10.17 Do not offer adjuvant radiotherapy to the axilla after axillary clearance for invasive breast cancer. [2009, amended 2018]

1.10.18 Offer adjuvant radiotherapy to the supraclavicular fossa to people with invasive breast cancer and 4 or more involved axillary lymph nodes. [2009]

1.10.19 Offer adjuvant radiotherapy to the supraclavicular fossa to people with invasive breast cancer and 1 to 3 positive lymph nodes if they have other poor prognostic factors (for example, T3 and/or histological grade 3 tumours) and good performance status. [2009]

1.10.20 Consider including the internal mammary chain within the nodal radiotherapy target for people with node‑positive (macrometastases) invasive breast cancer. [2018]

For a short explanation of why the committee made the 2018 recommendation and how it might affect practice, see the rationale and impact section on radiotherapy to nodal areas.

Full details of the evidence and the committee's discussion are in evidence review H: breast radiotherapy.

Intraoperative radiotherapy

1.11 Primary systemic therapy

Neoadjuvant chemotherapy

1.11.1 Offer neoadjuvant chemotherapy to people with ER‑negative invasive breast cancer as an option to reduce tumour size. [2018]

1.11.2 Offer neoadjuvant chemotherapy to people with HER2‑positive invasive breast cancer in line with the NICE technology appraisal guidance on pertuzumab for the neoadjuvant treatment of HER2‑positive breast cancer. [2018]

1.11.3 Consider neoadjuvant chemotherapy for people with ER‑positive invasive breast cancer as an option to reduce tumour size if chemotherapy is indicated. [2018]

For a short explanation why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on neoadjuvant chemotherapy.

Full details of the evidence and the committee's discussion are in evidence review J: neoadjuvant treatment of early and locally advanced breast cancer.

Neoadjuvant chemotherapy regimens

In July 2018, the use of platinums in recommendations 1.11.4 and 1.11.5 was off label. See NICE's information on prescribing medicines.

1.11.4 For people with triple‑negative invasive breast cancer, consider a neoadjuvant chemotherapy regimen that contains both a platinum and an anthracycline. [2018]

1.11.5 Discuss the benefits and risks of adding a platinum to an anthracycline‑containing neoadjuvant chemotherapy regimen. Topics to discuss include those in table 6, and particularly the risk of increased toxicity. [2018]

Table 6 Benefits and risks of adding a platinum to anthracycline‑containing neoadjuvant chemotherapy for triple‑negative invasive breast cancer

-

Effect of adding a platinum to anthracycline‑containing (with or without taxane) neoadjuvant chemotherapy

Effect on breast conservation rate

Adding a platinum improves response rates compared with anthracycline‑based (with or without taxane) chemotherapy. This may mean that some women who would otherwise need a mastectomy can be offered breast‑conserving surgery

Effect on pathological complete response rate (no residual cancer found at surgery)

Adding a platinum improves the chances of all signs of cancer disappearing in both the breast and lymph nodes in the armpit, compared with anthracycline‑based (with or without taxane) neoadjuvant chemotherapy

Effect on survival

No increase in overall survival with platinum‑based chemotherapy

Side effects

NOTE: Platinum‑based therapy is only suitable for fit patients with no significant comorbidities

Adding a platinum may mean that side effects are more severe. Anaemia, thrombocytopenia, neutropenia and febrile neutropenia are seen more frequently with platinum‑based chemotherapy

On average, if 1,000 women with triple‑negative breast cancer receive platinum‑containing neoadjuvant chemotherapy, about 70 additional women would experience severe or life‑threatening side effects compared with non‑platinum neoadjuvant chemotherapy

Bone marrow suppression and renal problems are likely in older people

Licensed status

At the time of publication (July 2018), platinums did not have UK marketing authorisation for this indication. See NICE's information on prescribing medicines.

For a short explanation why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on neoadjuvant chemotherapy regimens.

Full details of the evidence and the committee's discussion are in evidence review J: neoadjuvant treatment of early and locally advanced breast cancer.

Neoadjuvant endocrine therapy

1.11.6 Consider neoadjuvant endocrine therapy for postmenopausal women with ER‑positive invasive breast cancer as an option to reduce tumour size if there is no definite indication for chemotherapy. [2018]

1.11.7 Advise premenopausal women that neoadjuvant chemotherapy may be more likely to produce a clinical response than neoadjuvant endocrine therapy, but that some tumours do respond to neoadjuvant endocrine therapy. [2018]

1.11.8 Discuss with women the benefits and risks of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy. Topics to discuss include those in table 7. [2018]

Table 7 Benefits and risks of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy

-

Neoadjuvant endocrine therapy

Neoadjuvant chemotherapy

Definition

Tamoxifen or an aromatase inhibitor started before surgery

Only an option for women with ER‑positive breast cancer

Chemotherapy given before surgery

Only an option for people who would be recommended adjuvant (after surgery) chemotherapy

Administration

Tablet taken once a day at home

Intravenous administration in hospital, as an outpatient

Effectiveness

For postmenopausal women: may be as effective as neoadjuvant chemotherapy in terms of breast conservation rates and shrinking the tumour

For premenopausal women: less effective than neoadjuvant chemotherapy at shrinking the tumour (but some tumours may respond so may be effective in some women)

For postmenopausal women: effective at improving breast conservation rates and shrinking the tumour

For premenopausal women: more effective than endocrine therapy at shrinking the tumour

Potential disadvantages

If neoadjuvant endocrine therapy is not effective, then women may proceed to surgery earlier or may still need to have chemotherapy, either before or after surgery

-

Side effects

All endocrine therapies: menopausal symptoms such as hot flushes

For tamoxifen: increased risk of thrombosis and endometrial cancer

For aromatase inhibitors: joint and muscle pain, urogenital symptoms, bone density loss (may also occur with tamoxifen in premenopausal women)

Side effects are usually reversible

May allow women to avoid the additional side effects of chemotherapy (although women may still need adjuvant chemotherapy after surgery)

Side effects may include nausea and vomiting, risk of infections that may be life threatening, fatigue, neuropathy, cardiac toxicity, diarrhoea, constipation, sore mouth, skin and nail changes, risk of blood clots, risk of second malignancies, fluid retention, allergic reactions and hair loss

Side effects may persist long term

Fertility and family planning

Women should not become pregnant while taking tamoxifen, or within 2 months of stopping, because it may have adverse effects on the baby

Often causes temporary infertility

May cause permanent infertility

Length of course

May take longer than chemotherapy to shrink the tumour enough for breast‑conserving surgery

The duration of neoadjuvant chemotherapy is shorter than neoadjuvant endocrine therapy

For a short explanation why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on neoadjuvant endocrine therapy.

Full details of the evidence and the committee's discussion are in evidence review J: neoadjuvant treatment of early and locally advanced breast cancer.

Radiotherapy after neoadjuvant chemotherapy

1.11.9 Offer local treatment with mastectomy (or, in exceptional cases, breast‑conserving surgery) followed by radiotherapy to people with locally advanced or inflammatory breast cancer that has been treated with neoadjuvant chemotherapy. [2009]

1.11.10 Offer postmastectomy radiotherapy after neoadjuvant chemotherapy if post‑treatment histology shows node‑positive (macrometastases) breast cancer or involved resection margins. [2018]

1.11.11 Offer postmastectomy radiotherapy after neoadjuvant chemotherapy if pretreatment investigations show node‑positive (macrometastases) breast cancer. [2018]

1.11.12 Consider postmastectomy radiotherapy after neoadjuvant chemotherapy if post‑treatment histology shows node‑negative T3 breast cancer. [2018]

1.11.13 Consider postmastectomy radiotherapy after neoadjuvant chemotherapy if pretreatment investigations show node‑negative T3 breast cancer. [2018]

For a short explanation why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on radiotherapy after neoadjuvant chemotherapy.

Full details of the evidence and the committee's discussion are in evidence review J: neoadjuvant treatment of early and locally advanced breast cancer.

1.12 Complications of local treatment and menopausal symptoms

Lymphoedema

1.12.1 Inform people with breast cancer about the risk of developing lymphoedema, and give them relevant written information before treatment with surgery and radiotherapy. [2009]

1.12.2 Give advice on how to prevent infection that may cause or exacerbate lymphoedema to people who have had treatment for breast cancer. [2009, amended 2018]

1.12.3 When informing people with breast cancer about the risk of developing lymphoedema, advise them that:

  • they do not need to restrict their physical activity

  • there is no consistent evidence of increased risk of lymphoedema associated with air travel, travel to hot countries, manicures, hot‑tub use or sports injuries

  • there is no consistent evidence of increased risk of lymphoedema associated with medical procedures (for example, blood tests, injections, intravenous medicines and blood pressure measurement) on the treated side, and the decision to perform medical procedures using the arm on the treated side should depend on clinical need and the possibility of alternatives. [2018]

1.12.4 Ensure that people with breast cancer who develop lymphoedema have rapid access to a specialist lymphoedema service. [2009]

For a short explanation of why the committee made the 2018 recommendation and how it might affect practice, see the rationale and impact section on lymphoedema.

Full details of the evidence and the committee's discussion are in evidence review B: management of the positive axilla.

Arm mobility

1.12.5 All breast units should have written local guidelines agreed with the physiotherapy department for postoperative physiotherapy. [2009]

1.12.6 Identify pre‑existing shoulder conditions preoperatively in people with breast cancer, as this may inform further decisions on treatment. [2009]

1.12.7 Give instructions on functional exercises, which should start the day after surgery, to people with breast cancer. This should include relevant written information from a member of the breast or physiotherapy team. [2009]

1.12.8 Refer people to the physiotherapy department if they report a persistent reduction in arm and shoulder mobility after breast cancer treatment. [2009]

Menopausal symptoms

1.12.9 Stop systemic hormone replacement therapy (HRT) in women who are diagnosed with breast cancer. [2009]

1.12.10 Do not offer HRT (including oestrogen/progestogen combination) routinely to women with menopausal symptoms and a history of breast cancer. In exceptional circumstances, offer HRT to women with severe menopausal symptoms and with whom the associated risks have been discussed. [2009]

In July 2018, this was an off-label use of HRT, and HRT is contraindicated in women with a history of breast cancer. See NICE's information on prescribing medicines.

1.12.11 Offer women information and counselling about the possibility of early menopause and menopausal symptoms associated with breast cancer treatment. [2009]

1.12.12 Consider selective serotonin reuptake inhibitor (SSRI) antidepressants for women with breast cancer for relieving menopausal symptoms, particularly hot flushes, but not for those taking tamoxifen. For guidance on safe prescribing of antidepressants (such as SSRIs) and managing withdrawal, see NICE's guideline on medicines associated with dependence or withdrawal symptoms. [2009, amended 2018]

In July 2018, this was an off-label use of SSRIs. See NICE's information on prescribing medicines.

1.12.13 Do not offer soy (isoflavone), red clover, black cohosh, vitamin E or magnetic devices to treat menopausal symptoms in women with breast cancer. [2009]

1.13 Follow‑up

Follow‑up imaging

1.13.1 Offer annual mammography to all people with breast cancer, including DCIS, until they enter the NHS Breast Screening Programme (NHSBSP) in England or the Breast Test Wales Screening Programme (BTWSP) in Wales. People diagnosed with breast cancer who are already eligible for screening should have annual mammography for 5 years. [2009]

1.13.2 Do not offer mammography of the ipsilateral soft tissues after mastectomy. [2009]

1.13.3 Do not offer ultrasound or MRI for routine post‑treatment surveillance in people who have had treatment for invasive breast cancer or DCIS. [2009]

Clinical follow‑up

1.13.4 People who have had treatment for breast cancer should have an agreed, written care plan, which should be recorded by a named healthcare professional (or professionals). A copy should be sent to the GP and a copy given to the person. This plan should include:

  • designated named healthcare professionals

  • dates for review of any adjuvant therapy

  • details of surveillance mammography

  • signs and symptoms to look for and seek advice on

  • contact details for immediate referral to specialist care and

  • contact details for support services, for example, support for people with lymphoedema. [2009]

1.14 Lifestyle

1.14.1 Advise people with breast cancer that a healthy lifestyle is associated with a lower risk of recurrence, and that this should include:

1.14.2 For guidance on smoking cessation, see the NICE guideline on stop smoking interventions and services. [2018]

For a short explanation of why the committee made the 2018 recommendations and how they might affect practice, see the rationale and impact section on lifestyle.

Full details of the evidence and the committee's discussion are in evidence review K: lifestyle.

  • National Institute for Health and Care Excellence (NICE)