Rationale and impact
- Providing information and psychological support
- Surgery to the breast
- Evaluation and management of a positive axillary lymph node
- Breast reconstruction
- Predictive factors
- Adjuvant therapy planning
- Ovarian function suppression
- Extended endocrine therapy
- Endocrine therapy for ductal carcinoma in situ
- Adjuvant chemotherapy for invasive breast cancer
- Biological therapy
- Adjuvant bisphosphonate therapy
- Radiotherapy techniques
- Radiotherapy after breast‑conserving surgery
- Radiotherapy after mastectomy
- Radiotherapy to nodal areas
- Neoadjuvant chemotherapy
- Neoadjuvant chemotherapy regimens
- Neoadjuvant endocrine therapy
- Radiotherapy after neoadjuvant chemotherapy
These sections briefly explain why the committee made the recommendations and how they might affect practice. They link to details of the evidence and a full description of the committee's discussion.
The committee agreed, based on their clinical expertise, that continued improvement in breast cancer survival as well as post‑diagnosis quality of life needs ongoing research into new or refined treatment options to allow further optimisation of care.
People having treatment for breast cancer should be advised about options for preserving their fertility, so cross‑referred to the existing NICE guideline on this topic.
Recruitment into clinical trials wherever possible is already standard practice so the recommendation is unlikely to result in a change in practice.
Discussion of fertility options is already standard practice so the recommendation is unlikely to result in a change in practice.
There was some evidence that there was a reduced risk of ductal carcinoma in situ (DCIS) local recurrence if tissue margins were greater than 0 mm, so the committee recommended further surgery (re‑excision or mastectomy) to extend the margins if needed. Although there was no consistent evidence about tissue margins for invasive breast cancer, the committee agreed that further surgery should be offered.
The committee agreed that complete excision of the tumour with clear margins was essential for the high‑quality care of people with DCIS or invasive breast cancer.
Although there was evidence that aiming for wider margins reduced local recurrence, this did not improve overall survival. In addition, aiming for wider margins could lead to some people having unnecessary extra surgery. Given this uncertainty, the committee agreed the importance of personalised care and discussion to decide whether further surgery is needed.
There was not enough evidence to clearly define an optimum margin width between 0 mm and 2 mm to minimise local recurrence rates and minimise further surgery. So the committee agreed that this was an important topic for further research, and made a recommendation for research on the optimum tumour‑free margin width after surgery to the breast.
The rates of further surgery currently vary across the country. Although the committee noted that the recommendations will reinforce current best practice, there may be some centres that will need to amend their practice in order to follow these recommendations.
There was no new evidence that led the committee to change from the existing recommended practice (as recommended in the previous NICE guideline CG80) of:
offering axillary clearance to people with preoperatively pathologically proven involvement of the axillary lymph nodes
not offering axillary treatment after primary surgery to people with isolated tumour cells in their sentinel lymph nodes.
The committee agreed that current evidence shows that further axillary treatment after primary surgery does not improve survival for people with micrometastases and there are risks such as lymphoedema, therefore further treatment should not be offered to this population. There were unclear benefits and risks of further axillary treatment after primary surgery in people with only 1 or 2 sentinel lymph node macrometastases who have had breast‑conserving surgery and have been advised to have whole‑breast radiotherapy and systemic therapy, so the committee agreed that the risks and benefits of further treatment should be discussed with this group.
Studies of neoadjuvant therapy were excluded from the evidence review.
The committee agreed that the recommendations will result in a minor change in practice because some centres currently use mainly surgery and may not use radiotherapy. In addition, more time may need to be factored in to plan and deliver radiotherapy treatment.
There was not much good evidence, but the committee agreed that the main benefits of immediate breast reconstruction compared with delayed reconstruction are improved aesthetic satisfaction, improved symmetry, improved health‑related quality of life, lower overall rates of complications and a reduced need for further surgery. The committee agreed that in some circumstances, there are advantages to delayed reconstruction compared with immediate reconstruction (for example, reduced mastectomy flap loss, and capsular contracture). Therefore, delayed reconstruction should also be an option for women who wish to have a reconstruction after mastectomy. The committee also agreed that the option of no reconstruction should also be discussed, because this may be the preferred option for some women.
In addition, although radiotherapy can impact on outcomes after breast reconstruction, there was no consistent evidence for worse outcomes between radiotherapy delivered after immediate reconstructions compared with radiotherapy before delayed reconstructions. Therefore, the committee agreed that immediate reconstruction should be offered regardless of plans for chest wall radiotherapy.
There is little evidence regarding longer‑term outcomes and different types of reconstruction. Because of this, the committee agreed that more research is needed to understand whether immediate breast reconstruction or delayed breast reconstruction is better in women who may need postmastectomy radiotherapy. So they made a recommendation for research on long‑term outcomes for breast reconstruction in women having radiotherapy to the chest wall.
The recommendations may result in a substantial change in practice because many centres do not routinely offer immediate breast reconstruction to all women (especially those who have been advised to have radiotherapy). The impact will depend on how many immediate reconstructions are already carried out. In addition, the uptake of immediate breast reconstruction will also depend on women's preferences. There may be cost savings associated with immediate reconstructions because fewer surgical procedures are needed (reconstruction is done at the same time as mastectomy and there are lower rates of additional symmetrisation surgery).
There was not enough good evidence, so the committee agreed, using a formal consensus scoring system and their knowledge and experience, that progesterone receptor (PR) status should be assessed for all invasive breast cancers because:
it will help when tailoring adjuvant therapy
it will reduce delays in starting treatment
if people are already having testing at this stage, their PR status can be assessed without them having to wait for additional test results.
The committee also agreed that oestrogen receptor (ER), PR and human epidermal growth receptor 2 (HER2) status assessments should be requested simultaneously at the time of initial diagnosis to ensure that results are available at the initial preoperative multidisciplinary team meeting (as well as the postoperative meeting). This will avoid delays and the need for additional discussions.
Most people with invasive breast cancer have PR testing in current practice, although it is not always performed at diagnosis. The recommendations should reduce variation in practice and delays in starting treatment, and the need for pathology results to be discussed at more than 1 multidisciplinary meeting, and so may lead to a small cost‑saving.
Good evidence showed that the prognostic tool PREDICT is an accurate tool to estimate prognosis and the benefits of treatment in most people.
The committee agreed that most healthcare professionals already use the PREDICT tool, so this recommendation will not mean a big change in practice.
There was evidence that ovarian function suppression increased overall survival when combined with tamoxifen, and that women who have had chemotherapy benefited more. However, ovarian function suppression did not improve disease‑free survival. In addition, it induces a temporary menopause and can worsen the menopausal symptoms seen with tamoxifen.
Given the limited evidence of benefits and the side effects of the treatment, the committee agreed that healthcare professionals should discuss the potential benefits and risks with women. This will help women to decide which treatment is right for them.
There is variation among centres in the use of ovarian function suppression, so the recommendations should lead to greater consistency and improve access to the treatment, even though not all women will wish to have it. There will be an increase in required resources for centres that do not currently provide ovarian function suppression, because additional appointments will be needed to administer the medication and monitor side effects. However, this was not anticipated to be a substantial cost increase because of the number of centres already offering ovarian function suppression. Further, increased costs will be at least partially offset by improvements in survival outcomes.
Good evidence showed that switching to an aromatase inhibitor after 5 years of tamoxifen improved disease‑free survival compared with postmenopausal women who had only received tamoxifen for 5 years, with the benefits being greater in those women who had a greater risk of disease recurrence.
The evidence showed no benefit in terms of disease‑free survival or overall survival from continuing tamoxifen beyond 5 years. However, some of the studies on tamoxifen were conducted in the 1980s and may not be relevant to current practice. In the committee's experience, continuing tamoxifen can be beneficial for some women.
However, evidence showed that being on endocrine therapy for more than 5 years can increase the risk of problems such as endometrial cancer, osteoporosis, toxicity and phlebitis. The committee agreed that people will often prioritise survival even if this means they will have a reduced quality of life, but that people need to be informed about the possible benefits and risks so they can make a choice.
Because of the risk of problems with taking endocrine therapy for more than 5 years, the committee agreed that healthcare professionals should discuss the potential benefits and risks with women to help them make an informed choice about treatment, based on their own risk factors.
Some centres already review treatment at 5 years, and continue endocrine therapy with tamoxifen or an aromatase inhibitor when it could benefit women. Because a large number of women will be affected by these recommendations, the resource impact will be large for centres that are not currently providing treatment after 5 years.
There was good evidence that tamoxifen after breast‑conserving surgery for ER‑positive DCIS improved disease‑free survival and reduced rates of local recurrence in women who did not have radiotherapy. Because of their concerns about over‑treatment, the committee agreed that women who were at higher risk (those who should have had radiotherapy, but who did not receive it) would benefit more. There was no evidence available for aromatase inhibitors; however, the committee agreed they would likely produce similar improvements in disease‑free survival and reductions in local recurrence as tamoxifen. Therefore, the committee recommended endocrine therapy, rather than specifically tamoxifen.
The committee agreed that the benefits and risks of endocrine therapy should be discussed with the woman because of the potential treatment‑related complications such as menopausal symptoms, and the impact on family planning.
Offering endocrine therapy after initial treatment of DCIS will be a change of practice because it is not currently routinely offered to these women. However, because of the small number of people with DCIS who will not receive radiotherapy, and the low cost of the medicines, the committee agreed that the impact will not be significant.
There was good evidence of improved survival when taxanes are added to anthracycline‑based chemotherapy in people with node‑positive and node‑negative breast cancer. In both groups, the benefits and risks of treatment should be discussed because of the potential side effects associated with taxanes. Three‑weekly docetaxel was identified as a regimen with potentially more toxicity than weekly or fortnightly paclitaxel.
These recommendations may result in a substantial change in practice because of increased taxane use, particularly for people with node‑negative breast cancer and comorbidities.
In addition, there will be an increase in weekly and fortnightly chemotherapy regimens being offered (for people who cannot tolerate 3‑weekly regimens). These regimens have a higher cost because they are more resource intensive, and may affect capacity in chemotherapy services.
There was evidence that adjuvant trastuzumab can improve disease‑free survival and overall survival in some people with T1a and T1b HER2‑positive invasive breast cancer who were treated with adjuvant trastuzumab and chemotherapy. However, only a small number of people will benefit from this treatment and, because trastuzumab can cause heart problems, it is important to avoid offering it to people who do not need it. Because of this, the committee agreed that adjuvant trastuzumab should be an option for women with T1a and T1b tumours rather than a standard treatment.
Combined chemotherapy and trastuzumab was not found to be cost effective when compared to chemotherapy alone. However, the committee agreed that it was more appropriate to compare combined chemotherapy and trastuzumab with no treatment, because these are the strategies that are likely to be used in clinical practice. Because it is the HER2‑positivity that increases risk of recurrence for people with small (T1a and T1b) tumours, it does not make sense from a clinical perspective to not treat the component that is increasing risk (that is, trastuzumab treatment for HER2‑positivity). Further, the effect of chemotherapy alone in the economic model may be overestimated because the data may not fully reflect the population under consideration.
Currently, T1 tumours are not routinely treated with adjuvant trastuzumab, so this recommendation will lead to a change in practice. However, the committee agreed that the number of additional people having treatment would be small and so the impact on current practice would be minor and unlikely to require a substantial increase in resources.
There was good evidence that treatment with sodium clodronate and zoledronic acid improved disease‑free and overall survival in postmenopausal women with node‑positive invasive breast cancer.
There was little evidence of benefit for other bisphosphonates. The committee recommended considering zoledronic acid or sodium clodronate treatment for other high‑risk populations (such as postmenopausal women with node‑negative invasive breast cancer and a high risk of recurrence), based on the evidence that sodium clodronate has overall survival benefits in mixed populations.
Although there is evidence that intravenous (IV) bisphosphonates have a higher risk of osteonecrosis of the jaw, oral bisphosphonates have a higher risk of gastrointestinal problems. There is also a risk of atypical femoral fractures and osteonecrosis of the external auditory canal with bisphosphonates. Because each drug and regimen has different risks, the potential benefits and risks should be discussed with women to help them make an informed choice.
There was little evidence on survival, particularly for premenopausal women on ovarian suppression, those with node‑positive or node‑negative disease, and those with positive or negative oestrogen or progestogen statuses. There was not enough evidence to make a recommendation relating to the use of adjuvant bisphosphonates in premenopausal women. The committee agreed that further research is needed to determine the long‑term survival benefits and the groups of people most likely to benefit from adjuvant bisphosphonates. So they made a recommendation for research on groups of people who would benefit from the use of adjuvant bisphosphonates.
The committee did not look at the evidence relating to the use of bisphosphonates for bone health or for the use of baseline dual‑energy X‑ray absorptiometry (DEXA) scanning, so did not make any new recommendations.
Bisphosphonates are not consistently offered as adjuvant treatment, so this recommendation may lead to an increase in prescribing.
GPs may need to monitor people taking oral bisphosphonates, but this is likely to be an annual review so would not have a large workload impact. However, people may make more GP visits if they have side effects from bisphosphonate treatment.
The committee agreed that IV bisphosphonates would usually be administered at the same time as chemotherapy drugs for the first 6 months of treatment, so this would not result in extra hospital visits for this period. After that, extra visits for administration and monitoring may be needed.
There was good evidence that radiotherapy to the internal mammary nodes reduced locoregional recurrence and improved survival. However, the committee took into account the potential for lung and heart toxicity, so recommended using a radiotherapy technique that minimises this risk.
There was evidence that deep inspiratory breath‑hold radiotherapy techniques reduce the mean radiotherapy heart dose for adults with left‑sided invasive breast cancer receiving whole‑breast radiotherapy. The committee did not identify any harms. There was also evidence that deep inspiration breath‑hold radiotherapy techniques did not reduce the target coverage of whole‑breast radiotherapy.
There was no evidence about the use of deep inspiration breath‑hold radiotherapy techniques for people with right‑sided breast cancer, so the committee did not make separate recommendations for this subgroup.
Using a radiotherapy technique that minimises the dose to the lung and heart is likely to need a change in practice for many centres. There will be some impact on resources in order to implement this recommendation because additional training will be needed and local protocols will need developing. However, the long‑term impact on resources will be minimal: some additional planning time will be needed but there is no impact on the length or number of radiotherapy sessions.
Currently, deep inspiratory breath‑hold radiotherapy techniques are not routinely offered to people with invasive breast cancer having whole‑breast radiotherapy. However, the committee noted that the Royal College of Radiologists has produced consensus statements that advise using this technique, and that many centres already offer it. The recommendation will ensure consistent practice and ensure that people can access the best care.
There is evidence that whole‑breast radiotherapy after breast‑conserving surgery reduces the risk of recurrence and increases overall survival. It also decreases rates of depression and anxiety.
However, because the risk of breast cancer recurring at 5 years is very low and there are harms associated with radiotherapy, the benefits of radiotherapy for women with a very low risk of recurrence are less certain. For these women, the committee agreed that healthcare professionals should fully discuss the benefits and risks with women before a decision is made.
Good evidence showed that partial breast radiotherapy led to similar results to whole‑breast radiotherapy after breast‑conserving surgery in women with a low risk of local recurrence. In addition, it may have fewer treatment‑related adverse effects. There was evidence for multicatheter interstitial brachytherapy but this was not recommended because it is not currently available in England.
Most women are already offered radiotherapy after breast‑conserving surgery so this reflects current practice, but more time may be needed to discuss the balance of benefits and risks with women.
The committee was aware that current practice for external beam partial breast radiotherapy after breast‑conserving surgery is based on the Royal College of Radiologists' 2016 consensus statement, so there would be no change to recommended practice.
The committee agreed that adjuvant postmastectomy radiotherapy should be offered to people who have macroscopically node‑positive invasive breast cancer or have involved resection margins. This is because the evidence showed a beneficial effect on survival and local recurrence. Although the evidence was limited and the committee acknowledged that radiotherapy is associated with lung and cardiac morbidity, they concluded that for this group of women, the benefits of radiotherapy outweigh the harms.
There was evidence of a beneficial effect of postmastectomy radiotherapy on local recurrence and overall survival for people with node‑negative invasive breast cancer. However, the committee agreed that there was a risk of over‑treatment if all people with node‑negative invasive breast cancer received postmastectomy radiotherapy. Therefore, the committee recommended that adjuvant postmastectomy radiotherapy should be considered for people with node‑negative T3 or T4 invasive breast cancer. There was no evidence for this specific subgroup but they would be considered at increased risk of recurrence and mortality relative to smaller, node‑negative invasive breast cancers because of the size of the tumour.
The committee agreed that radiotherapy after mastectomy should not be offered to women with early invasive breast cancer who are at low risk of local recurrence (for example, most women who are lymph node‑negative) because the evidence showed limited benefit in survival and local recurrence.
The committee agreed that the recommendations will reinforce current practice, so there would be little change in practice.
There was good evidence that radiotherapy to the internal mammary nodes reduced locoregional recurrence and improved survival. However, the committee took into account the potential for lung and heart toxicity, and agreed the importance of using a radiotherapy technique that minimises this risk.
This recommendation is likely to need a change in practice for many centres. There will be some impact on resources in order to implement this recommendation because additional training will be needed and local protocols will need developing. However, the long‑term impact on resources will be minimal: some additional planning time will be needed but there is no impact on the length or number of radiotherapy sessions.
There was good evidence to say that having chemotherapy before surgery (neoadjuvant chemotherapy) enables some women to have breast‑conserving surgery who would otherwise have had total removal of their breast. The committee agreed that the response to neoadjuvant therapy could help to guide the choice of subsequent adjuvant therapy.
The committee agreed that the recommendations would not result in a major change in practice because neoadjuvant chemotherapy is already offered in many centres. These recommendations will help improve consistency in practice.
There was evidence that platinum‑containing neoadjuvant chemotherapy regimens can improve pathological complete response (pCR) rate and breast conservation rate in people with triple‑negative invasive breast cancer. However, the committee took into account that platinum‑containing regimens can cause anaemia, thrombocytopenia, neutropenia and febrile neutropenia, and bone marrow problems and renal problems in older people. The committee agreed that healthcare professionals should have a full discussion with people about the benefits and risks of these regimens.
There was no evidence on people with the BRCA germline mutation, so the committee did not make separate recommendations for this subgroup.
Currently, platinum‑containing neoadjuvant chemotherapy is not routinely offered to people with triple‑negative early and locally advanced breast cancer, although the committee was aware that some centres may offer it. The recommendations will therefore bring a change in practice and will make practice more consistent across the NHS. The committee estimated that approximately 30–40% of people receiving neoadjuvant chemotherapy may be affected by this recommendation.
For postmenopausal women, there was some evidence that breast conservation rates, changes in tumour size and overall survival are the same with neoadjuvant endocrine therapy and neoadjuvant chemotherapy. Endocrine therapy is safer and has fewer side effects than chemotherapy, but there was not enough evidence to recommend endocrine therapy over chemotherapy for every woman. The committee agreed that healthcare professionals should discuss the potential benefits and risks with women, to help them decide which treatment is right for them and that more research is needed to say whether neoadjuvant endocrine therapy is as effective as neoadjuvant chemotherapy.
The evidence for premenopausal women showed that neoadjuvant chemotherapy was more effective than endocrine therapy, but that endocrine therapy may be effective in some women. However, some women may prefer endocrine therapy because it is safer and has fewer side effects. Because of this, the committee agreed that healthcare professionals should discuss the potential benefits and risks with women, to help them decide which treatment is right for them. The committee agreed that more research is needed on the long‑term safety of neoadjuvant endocrine therapy, and to identify which premenopausal women will benefit from it. So they made recommendations for research on the safety of neoadjuvant endocrine therapy in premenopausal women and postmenopausal women with early breast cancer.
Neoadjuvant endocrine therapy is already being used, although there may be an increase in the number of people being offered it.
There was not enough evidence to recommend subgroups of women in whom postmastectomy radiotherapy could be safely omitted after neoadjuvant chemotherapy. Therefore, the committee agreed that the recommendations for postmastectomy radiotherapy among people who have not received neoadjuvant chemotherapy applied to this population.
People with node‑negative T4 cancer were not included in this review because they are covered by the recommendation from the previous guideline which has been retained.
Women who respond well to neoadjuvant chemotherapy may derive less benefit from radiotherapy, but the committee agreed that further research was required to determine if the risks of radiotherapy outweighed the benefits in some women. So they made a recommendation for research on the indications for postmastectomy radiotherapy after neoadjuvant chemotherapy.
The committee noted that decisions about postmastectomy radiotherapy after neoadjuvant chemotherapy are currently based on pretreatment investigations, so there will be no change to practice.
Good evidence showed that there is no increased risk of lymphoedema associated with maintaining exercise levels after axillary intervention, so the committee agreed that people should not restrict or avoid physical activity.
Although the evidence was limited and mixed, the committee concluded that there is no consistent evidence of increased risk of lymphoedema associated with air travel, travel to hot countries, manicures, hot‑tub use, sports injuries, or medical procedures on the treated side.
Advice about preventing lymphoedema is already being provided as part of routine care, so there is unlikely to be much change in practice. However, the recommendation will lead to greater consistency in the advice offered. It should also reduce inequality and improve the quality of standard care if people who have had axillary treatment need immunisations or elective procedures.
There was evidence that both dietary changes (reducing fat intake and maintaining a healthy weight) and physical activity increase survival in people with invasive breast cancer.
There was some evidence that cancer recurrence is more likely in people who drink more than 3 or 4 alcoholic drinks per week or 6 g of alcohol per day. This equates to approximately 5 units of alcohol per week.
There was no evidence that smoking cessation reduces recurrence of breast cancer, although the view of the committee was that smoking cessation should always be recommended to people with breast cancer.
The committee discussed that many NHS services would already be advising people with breast cancer about the importance of a healthy lifestyle, and how they can make lifestyle changes to reduce the risk of recurrence. The committee agreed that these recommendations will help to direct conversations towards effective lifestyle changes. There will be no impact on resources because these discussions were already happening, and most of the lifestyle changes will be 'self‑care' and implemented by patients themselves.