Narrative review
Cancer Surgery
Volume 207 - Issue 5

Radiation therapy and early breast cancer: current controversies

Author:  John Boyages

Med J Aust 2017; 207 (5): 216-222. || doi: 10.5694/mja16.01020
Published online: 4 September 2017

Recent advances are likely to further improve the incremental benefit of radiation over and above surgery and systemic therapy and thus increase survival rates

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Summary

 

  • Radiation therapy (RT) is an important component of breast cancer treatment.
  • RT reduces local recurrence and breast cancer mortality after breast conservation for all patients and for node-positive patients after a mastectomy.
  • Short courses of RT over 3–4 weeks are generally as effective as longer courses.
  • A patient subgroup where RT can be avoided after conservative surgery has not been consistently identified.
  • A radiation boost reduces the risk of a recurrence in the breast but may be omitted for older patients with good prognosis tumours with clear margins.
  • Axillary recurrences can take a long time to appear, with 35% occurring after 5 years.
  • Leaving disease untreated in regional nodes is associated with reduced survival.
  • Not all patients require radiation after neoadjuvant chemotherapy and a subsequent mastectomy.
  • Modern RT equipment and techniques will further improve survival rates.

 

A year after Wilhelm Röntgen discovered x-rays in 1895, radiation was used by Emil Grubbé in Chicago to treat a patient with inoperable breast cancer, applying radiation energies that could penetrate at most a superficial skin cancer today.1 In the 1920s, radium was used following conservative surgery by Geoffrey Keynes at St Bartholomew’s Hospital, London, producing equivalent survival rates to radical mastectomy, which was introduced by William Halsted in the late 19th century.2,3

After World War 1, deep x-ray therapy was introduced, with energies up to 200 kV. Megavoltage linear accelerators and cobalt beam were largely introduced in the 1960s.4 However, radiation therapy (RT) remained imprecise, with lower energies causing severe skin reactions, and planning involving surface anatomy, gentian violet marks and tracing paper, rather than the sophisticated imaging and 3D computing techniques of today.

With more effective chemotherapies and hormonal and targeted therapies, controversy exists as to whether RT can be reduced in extent or avoided altogether after surgery for early breast cancer given that RT after breast conservation or a mastectomy reduces recurrence rates and improves survival (Box 1).5,6 After conservative surgery, RT to the breast halves the overall recurrence rate and reduces breast cancer mortality by about one-sixth.5 Cosmetic results are excellent if limited surgery is combined with moderate dose radiation.

Substantial changes in practice have occurred since these clinical trials were completed and their results may not be totally applicable today. Many women now have smaller screen-detected cancers and radiotherapy techniques better target the cancer while protecting normal structures such as the heart. Serial sectioning of sentinel nodes and more frequent recognition of micrometastases has meant that some women classified as node-negative in earlier studies would have been identified as node-positive and given better systemic therapy if treated today. Therefore, the challenge is to integrate historical data with our better understanding of disease biology and treatments to formulate a personalised treatment strategy.

Radiation after conservative surgery

Several trials firstly attempted conservative surgery with or without RT and later with or without hormonal treatment, usually tamoxifen. Although recent trials have reported lower recurrence rates, this is partly due to shorter follow-up and better patient selection and may not generally apply to a community setting. A meta-analysis found that older patients with small, low grade, oestrogen-receptor (ER)-positive tumours have a low recurrence rate and are possible candidates for omitting RT in some clinical circumstances,5 and other researchers have tested accelerated partial breast irradiation in this low risk group.7

Box 2 shows recent trials of lower risk older patients with small, ER-positive, node-negative tumours randomised between conservative surgery with or without RT and/or hormonal treatment.8-14 Adjuvant hormonal treatment reduces the risk of an in-breast recurrence when compared with surgery alone, but the combination of RT with or without hormonal treatment is more effective and more sustainable.

The question remains as to the lesser of two evils. For an 80-year-old with 10.2 years average life expectancy15 with a small ER-positive tumour, is it best to advise 5 years of tamoxifen with potential side effects including a small risk of mortality from thromboembolic disease, or a 3-week course of RT with a small risk of recurrence?16-18 This is the art of oncology — working out a personalised plan based on listening to the patient to find the right solution for their time of life. For a frailer patient, starting with hormonal treatment such as an aromatase inhibitor (with less thrombosis risk) and avoiding surgery or RT is another option, but 5-year local recurrence rates are as high as 70%.19,20 Therefore, this known development of tumour resistance remains a concern for fitter patients treated with conservative surgery and tamoxifen without radiation.

Shorter courses of radiation

Hypofractionation means a shorter radiation course with higher daily doses for the same biological effect. This saves the patient time and money and reduces pressure on public radiotherapy units. The United Kingdom Standardisation of Breast Radiotherapy (START) trial A compared a standard regimen of 50 Gy in 25 fractions with 41.6 Gy or 39 Gy in 13 fractions all over 5 weeks. In START trial B, 50 Gy in 25 fractions over 5 weeks was compared with 40 Gy in 15 fractions over 3 weeks.21 A Canadian trial for node- and margin-negative disease compared 42.5 Gy in 16 fractions over 3 weeks to 50 Gy in 25 fractions over 5 weeks.22 Boost was optional in the UK trials and omitted in the Canadian trial. Shorter schedules were not inferior for local recurrence or survival except for high grade tumours (15.6%, 10-year local recurrence) compared with the control group (4.7%; P = 0.01), perhaps due to the lack of a radiation boost in the Canadian trial.22 More detailed analysis and longer follow-up of the Canadian study found that grade on its own did not influence local recurrence, which was lower for low grade ER-positive tumours (4.5%) and higher grade triple-negative breast cancer (4.5%), but significantly higher (P < 0.001) for higher grade ER-positive tumours (7.9%) and human epidermal growth factor receptor 2 (HER2)-positive tumours (6.9%).23 The START trials did not show a higher local recurrence rate in higher grade tumours, perhaps because 61% received an additional RT boost.

In practice, standard fractionation appears to be better for larger breasted women for whom increased breast oedema can be a problem. It remains to be seen if this can be reduced with more sophisticated radiation techniques. The Canadian trial excluded women with large breasts, few women received chemotherapy and nodal radiation was not given.22 In the START trials, cosmetic result was not inferior for larger breasted women, but only a small fraction were in this group (15.6%).21

In START trial A, one patient (0.1%) who received 41.6 Gy in 13 fractions developed brachial plexopathy;21 a concern for faster schedules involving nodal irradiation, particularly if neurotoxic chemotherapeutic agents such as the taxanes are also used. The Australian and United States guidelines recommend hypofractionated treatment only for patients aged 50 years or older, with node-negative tumours up to 5 cm and no chemotherapy and where breast size and treatment technique minimise dose variation across the volume.24,25 The Australian guidelines also advise caution when recommending this approach to other patients. The UK NICE guidelines recommend that all patients with early invasive breast cancer after breast-conserving surgery receive 40 Gy in 15 fractions.26

The utility of accelerated partial breast irradiation is not yet entirely clear. This type of radiation can be delivered using intra-operative electron beam, placement of radioactive guide wires that can be loaded post-operatively, or targeted external beam radiation. A review of these techniques has been addressed elsewhere.27 Recent trials add to the debate by using intracavitary brachytherapy, or 3D conformal accelerated partial breast irradiation to deliver radiation in shorter periods to the at-risk primary tumour area.28,29

Boost to the primary tumour site

Detailed pathological studies done in the 1980s found that cancer cells were often located as far as 4 cm away from the edge of the primary tumour and this was often ductal carcinoma in situ.30 Further, early studies of the pattern of recurrence after conservative surgery and RT found that 60–70% occurred at the primary site,31,32 identifying this as an important focus for clinical examination, additional mammographic views, ultrasound and non-surgical biopsy after treatment. Predictive factors for local recurrence included young age at diagnosis, lymphatic vessel invasion, an extensive intraductal component and a positive margin, leading to studies of surgical extent, margin width and radiation boost dose31-34 in an attempt to improve local control rates. A European trial of over 5000 patients reported a 20-year breast tumour recurrence rate of 16.4% in the no-boost group compared with 12.0% in the boost group (P < 0.0001).35 This study found that the boost significantly reduced the risk of a recurrence for young patients or those with grade 3 tumours or an extensive intraductal component. For the patient subgroup with grade 3 ER-negative tumours, the boost reduced the risk of breast tumour recurrence from 31% to 5% (P = 0.01), highlighting the need to strongly consider a boost for this scenario irrespective of fractionation schedule.36

Local recurrence rates have fallen and not all patients require a boost.18,37,38 Recent US guidelines on surgical margins recommended “no ink at the margin” to mean a negative margin, rather than a specific margin width of 1 or 2 mm. This should reduce unnecessary re-excisions for many patients.37,39,40 Early results from a large Danish study of 11 900 patients found no evidence of improved local control by margin depth.41 A previous study found that patients treated without a boost (usually because of a large excision specimen or a negative re-excision) had no increase in the risk of local recurrence compared with patients who did receive a boost.31

In practice, the surgeon can assist boost planning by placing titanium clips at the excision borders. The radiation oncologist must correlate margin depth with pre-operative imaging and pathological predictors for local recurrence and sometimes consider post-operative mammography or magnetic resonance imaging. It is insufficient simply to boost the scar, because with modern oncoplastic techniques, the scar often has no relationship to the actual primary tumour site where the risk of recurrence is highest.42 Different boost techniques include electron beam, which creates more skin reaction, or an external photon boost, which may involve treating more normal tissue or more localised synchronous boost techniques.

Radiation therapy after neoadjuvant chemotherapy

The use of post-mastectomy RT is widely accepted for patients with four or more positive nodes but there is still controversy about its use in patients with one to three positive nodes43 or after neoadjuvant chemotherapy. Today, chemotherapy is used for patients with larger tumours not only to reduce tumour size to facilitate breast conservation but also to assess in vivo tumour response to the chosen chemotherapy. Patients with HER2-positive disease may receive trastuzumab in addition to chemotherapy.

A 2012 study used National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 and B-27 trial data to identify patient subgroups with a low rate of loco-regional recurrence after neoadjuvant chemotherapy and mastectomy and no RT.44 Cohorts with a less than 10–12% risk of loco-regional recurrence had pathologically negative nodes after neoadjuvant chemotherapy irrespective of whether or not they presented with clinically node-positive or -negative disease or had larger tumours.44 Chemotherapy can reduce the likelihood of pathological nodal disease, but the reductions are not large, particularly for lower grade tumours. In the NSABP B-18 trial, patients randomised to four cycles of doxorubicin and cyclophosphamide after an axillary clearance had a 57% node-positivity rate, compared with 41% for patients who had a clearance after neoadjuvant doxorubicin and cyclophosphamide.45 The addition of a taxane to doxorubicin and cyclophosphamide in the NSABP B27 study increased the overall pathological complete response rate from 14% to 26% (P < 0.001).46 Pathological complete response rate was significantly higher for patients with triple-negative (38.2%) or HER2-positive (45.4%) tumours than for patients with ER-receptor-positive, HER2-negative disease (11.4%) (P < 0.0001).47 One review suggested that clinical stage II (T1-2 N0–N1) patients aged over 40 years, with ER-positive disease and no lymphatic vessel invasion who have a pathological complete response rate or 0–3 positive axillary nodes without cancer extending beyond the lymph node capsule, gain little or no benefit from post-mastectomy RT after neoadjuvant chemotherapy.48

The pre-operative classification of breast cancer by molecular subtypes has influenced not only the response to chemotherapy, but also the choice of systemic agent. It also helps to predict the risk of recurrence. It is well known, for example, that invasive lobular carcinomas have a low pathological complete response rate (4.9%) to neoadjuvant chemotherapy compared with invasive ductal carcinoma (20.2%) (P < 0.0001).49 Residual lobular carcinoma can be hard for the pathologist to detect and can infiltrate the skin. This makes clinical detection difficult, so post-mastectomy RT is usually indicated. It is less well known that patients with triple-negative disease have better loco-regional control rates with conservative surgery and RT than with mastectomy alone.50-52 Further, not all node-negative patients with a tumour over 5 cm (T3 N0) require post-mastectomy radiation.53 Ongoing trials are investigating the role of post-mastectomy RT in patients receiving neoadjuvant chemotherapy.54 Pre-operative assessment by a radiation oncologist can help with decision making and subsequent field placements.

Regional node irradiation after positive axillary sentinel node

There is increasing long term data showing that any cells in a sentinel node reduce survival, including isolated tumour cells, micrometastases or larger deposits, although this remains an area of debate in the era of more effective systemic therapy.55 The risk of a non-sentinel node metastasis largely depends on the thoroughness of the subsequent axillary dissection. In a consecutive validation study at Westmead Hospital, Sydney,56 140 patients underwent a complete axillary dissection (mean of 22 nodes dissected) after a sentinel node biopsy, including nodes in level 3 inferior to the medial end of the clavicle and involving three surgeons; other validation studies usually had less complete axillary dissections and multiple surgeons, potentially underestimating the true rate of non-sentinel node metastasis.57 Of 51 patients with a positive sentinel node, 47% had non-sentinel node metastases. Primary tumour size was the only significant predictor for non-sentinel node involvement; 25% of patients with a primary tumour size = 20 mm and 67% with a primary tumour size > 20 mm had additional disease in the axilla (P = 0.005).56

The American College of Surgeons Oncology Group Z0011 trial randomised older patients with predominantly small (69% T1), grade 1 and 2 (72%) ER-positive tumours who underwent conservative surgery and RT to an axillary dissection or observation after a positive sentinel lymph node biopsy.57,58 Patients were treated with RT to the breast alone. Nodal positivity was micrometastatic in 45% of the sentinel lymph node biopsy group and 38% in the dissection group. After an axillary dissection, 27% had additional positive axillary nodes. Nearly all patients received systemic therapy. Regional nodal failure rate at 10 years was 0.5% in the nodal dissection group and 1.5% in the sentinel lymph node biopsy group (P = 0.28).

Unfortunately, clinicians have applied the Z0011 trial results in clinical scenarios outside the strict study entry criteria, including the post-mastectomy setting. Micrometastases have been observed in a small subgroup of patients after a mastectomy,59 but current guidelines caution against not dissecting the axilla if radiation is not given.60 Of concern, 35% of axillary recurrences occur after 5 years and late recurrences cause significant morbidity.5 Further, a retrospective audit found 69% of patients in the Z0011 trial received radiation that treated the lymph nodes.61 In many ways, the Z0011 study compared axillary radiation with axillary surgery, which is known to be equivalent.62

A randomised trial compared axillary and supraclavicular fossa radiation after a positive sentinel node to axillary dissection and found no difference in outcome except for less arm oedema (11% v 23%; P < 0.0001) in the RT group.63 The 5-year axillary recurrence rate was 0.4% in the axillary dissection group and 1.2% in the nodal radiation group, with no survival difference. This approach would avoid a second operation to the axilla for selected patients with limited isolated tumour cells or micrometastases after a sentinel node biopsy.63

However, treatment to the full axilla can also be personalised based on the risk of non-sentinel node involvement and prognostic features of the tumour. High-tangent RT encompassing levels 1 and 2 of the axilla is an option if the risk is low (eg, ER-positive tumour, primary tumour = 20 mm, no lymphatic vessel invasion, single micrometastasis), whereas comprehensive regional node irradiation is preferred if the patient has grade 3 tumours, extensive lymphatic vessel invasion and more than one sentinel node involved.64 In some patients with high grade, triple-negative or HER2-positive disease, a post-operative positron emission tomography scan (Box 3, A and B) may help determine treatment strategy. Various calculators are available to determine the probability of non-sentinel node involvement to guide therapy (eg, http://nomograms.mskcc.org/breast/BreastAdditionalNonSLNMetastasesPage.aspx).

In summary, leaving a small burden of axillary disease after a sentinel node biopsy is not unreasonable in most situations, provided radiation to the regional nodes is added.

The internal mammary chain

In 1918, Stibbe documented that the first to sixth intercostal mammary spaces contained lymph nodes in 97%, 98%, 83%, 9%, 13% and 63% of cases respectively;65 other studies have found lymph nodes to be as infrequent as 10% in the sixth space.66 The nodes lie medial to the internal mammary chain (IMC) vessels in 88%, 76% and 21% respectively in the first three interspaces and laterally thereafter.65 Coombs and colleagues highlighted the dilemma of a lymphoscintigram draining to the IMC.67 Involvement of cancer in biopsied IMC sentinel lymph nodes was 22.2% but increased significantly to over 35% for risk factors such as high grade, lymphatic vessel invasion or medial tumours with a positive axillary sentinel node. IMC recurrence is uncommon but morbid, and causes destruction of the sternum and adjacent ribs (Box 3, C).

IMC RT has been shown to reduce distant metastases and potentially improve survival (Box 1 and Box 4).5,6,68-73 For example, the MA.20 trial randomised patients with node-positive or high risk, node-negative disease treated with conservative surgery and RT to additional RT to the regional nodes including the IMC.69 Distant metastasis rates were 12.9% in the nodal irradiation group and 16.5% in the control group (P = 0.03), with no difference in breast cancer mortality. Patients with ER-negative disease who received IMC RT had a lower 10-year mortality rate than patients who did not receive IMC RT (18.7% v 26.1%; P = 0.05). Other trials show similar findings and support the notion that leaving IMC disease behind is probably detrimental to survival and that this area should be selectively treated using RT (Box 4).43

IMC radiation is problematical because it potentially increases heart dose, morbidity and mortality. There have been significant advances in RT technology, with sophisticated imaging integrated into planning systems using techniques that protect the heart with shielding or deep inspiration breath holding (Box 5), preferably using volumetric modulated arc therapy (Box 6). Volumetric modulated arc therapy can achieve highly conformal dose distributions by rotating the linear accelerator gantry at varying speeds through one or more arcs while simultaneously changing the field shape. This allows shaping or sculpting radiation doses to complex cancer volumes, while using modern equipment with on-board computed tomography scans with treatment times of about 5 minutes to reduce the dose to normal structures such as the heart. These advances are likely to further improve the incremental benefit of radiation over and above surgery and systemic therapy and thus increase survival rates.

Box 1 – Meta-analyses of randomised trials of breast-conserving surgery or mastectomy with or without radiation therapy (RT)5,6

 

No. of patients

Treatment

Any first recurrence

Loco-regional recurrence at 10 years

Breast cancer mortality at 15–20 years*

Loco-regional recurrence reduction with RT

Breast cancer mortality reduction with RT

Conservative surgery ± RT

 

 

 

 

 

 

 

All

10 801

No RT

35.0%

25.1%

25.2%

 

 

 

 

RT

19.3%

7.7%

21.4%

17.4%†

3.8%‡

pN0

7287

No RT

31.0%

22.8%

20.5%

 

 

 

 

RT

15.6%

7.3%

17.2%

15.5%†

3.3%‡

pN+

1050

No RT

63.7%

43.0%

51.3%

 

 

 

 

RT

42.5%

12.4%

42.8%

30.6%†

8.5%‡

Mastectomy ± RT

 

 

 

 

 

 

 

pN+

3131

No RT

62.5%

26.0%

66.4%

 

 

 

 

RT

51.9%

8.1%

58.3%

17.9%†

8.1%‡

pN0

700

No RT

21.1%

1.6%

26.6%

 

 

 

 

RT

22.4%

3.0%

28.8%

- 1.4%§

- 2.2%§

1–3 pN+

1314

No RT

45.7%

20.3%

50.2%

 

 

 

 

RT

34.2%

3.8%

42.3%

16.5%†

7.9%‡

> 4 pN+

1772

No RT

75.1%

32.1%

80.0%

 

 

 

 

RT

66.3

13.0%

70.7%

19.1%†

9.3%‡

pN0 = pathologically node-negative. pN+ = pathologically node-positive. * Breast cancer mortality was at 15 years for conservative surgery and 20 years for mastectomy. † * P < 0.00001. ‡ P < 0.05. § Not significant.

Box 2 – Recent trials of older patients with small node-negative cancers treated with surgery with or without radiation therapy (RT) and hormone therapy (HT)*

Study

First year

No. of patients

Age = 50 years

Tumour = 20 mm

Hormonal treatment†

Follow-up (years)

Ipsilateral breast tumour recurrence after conservative surgery

Nil

HT

RT

RT + HT

Fisher 20028

1989

1000

80%

98%

67%

7.2

 

16.5%

9.3%

2.8%

Winzer 20049

1991

361

91%

99%

50%

5.9

15.7%

2.8%

3.7%

3.8%

Fyles 200410

1992

769

100%

83%

50%

5.6

 

7.7%

 

0.6%

Hughes 200411

1994

636

100%

100%

50%

12.6

 

4.4%

 

0.6%

Potter 200712

1996

869

97%

93%

100%

4.5

 

5.1%

 

0.4%

Blamey 201313

1992

1135

ns

100%

50%

13.9

 

10.2%

 

3.9%

Kunkler 201514

2003

1326

100%

88%

50%

5

 

4.1%

 

1.3%

ns = not specified. * None of the studies used chemotherapy and patients were pathologically (and a few clinically) node-negative. † Tamoxifen (20 mg daily for 5 years) was the standard adjuvant endocrine treatment, but some studies (eg, Kunkler 2015)14 allowed other forms of adjuvant or neoadjuvant endocrine treatment. About 50% of patients in Potter 200712 received anastrozole.

Box 3 – Positron emission tomography (PET) scans

A: Hot internal mammary chain (IMC) node on post-operative PET scan. B: Persistent hot node in axilla level 1 in post-operative PET scan after sentinel node showed micrometastasis. C: Left-sided IMC recurrence 10 years after mastectomy and 2 years after stopping hormonal treatment for a 55 mm invasive lobular carcinoma of the upper inner quadrant. Images courtesy of Macquarie Medical Imaging.

Box 4 – Trials of patients treated with breast conservation or mastectomy with or without internal mammary chain (IMC) radiation therapy (RT)

Study

First year

No. of patients

Median follow-up (years)

= 4 pN+

pN0

RT location

Distant metastases

Benefit from RT

No IMC RT

IMC RT

Thorsen 201668*

2003

3089

8.9

41.1%

0

Breast/chest wall, SCF, ICF, axilla II + III (axilla I if > 6 N+) + IMC (I-IV) if right-sided

29.7%

27.4%

2.3%

Whelan 201569†

2000

1832

9.5

5.3%

9.7%

Breast ± SCF, axilla III, axilla I + II if < 10 nodes dissected or > 3N+ and IMC (I–III)

16.5%

12.9%

3.6%

Bartelink 201535†

1996

4004

10.9

12.5%

44.4%

Breast/chest wall ± SCF and IMC (I–III or I–IV if lower inner quadrant)

19.6%

15.9%

3.7%

Hennequin 201370†

1991

1334

11.3

31.1%

24.8%

Chest wall and SCF ± IMC (I–V)

39.9%

35.2%

4.7%

Chang 201371‡

1994

396

12.4

84.0%

4.3%

Chest wall + SCF ± IMC (I–VI)

42.7%

35%

7.7%

Courdi 201372‡

1975

2558

12.8

0

100%

Breast ± SCF, ± IMC (I–IV)

18.4%

8.1%

10.3%

ICF = intercondylar fossa. pN+ = pathologically node-positive. pN0 = pathologically node-negative. SCF = supraclavicular fossa. * Prospective non-randomised trial. † Randomised controlled trial. ‡ Case series.

Box 5 – Fused image showing heart covered by radiation beam (normal breathing, green arrow) and missed after deep inspiration (orange arrow); primary tumour site marked at surgery by titanium clips (yellow arrow)

Reproduced with permission from the Royal Australian College of General Practitioners from Tailby E, Boyages J. Conservation surgery and radiation therapy in early breast cancer – an update. Aust Fam Physician 2017; 46: 214-219. www.racgp.org.au/afp/2017/april/conservation-surgery-and-radiation-therapy-in-early-breast-cancer-an-update. Image courtesy of Genesis Cancer Care.

Box 6 – Volumetric modulated arc therapy plan of a patient who underwent a left nipple-sparing mastectomy for a triple-negative breast cancer and prophylactic right mastectomy

A: Axial slice. B: Sagittal slice. C: Coronal slice. D: 3D volume render. Shading: green, internal mammary chain volume; yellow, axilla level 1; light blue, supraclavicular fossa; red, heart; blue, 47.5 Gy dose cloud. Reproduced with permission from the Royal Australian College of General Practitioners from Tailby E, Boyages J. Conservation surgery and radiation therapy in early breast cancer – an update. Aust Fam Physician 2017; 46: 214-219. www.racgp.org.au/afp/2017/april/conservation-surgery-and-radiation-therapy-in-early-breast-cancer-an-update. Images courtesy of Genesis Cancer Care.

Author

  • John Boyages
  • 1. Macquarie University, Sydney, NSW

Correspondence: john.boyages@mq.edu.au

Competing interests

No relevant disclosures.

Acknowledgements

I thank Ellen Tailby for research assistance, Philippa Sutton for editing and managing earlier versions of the manuscript, and Sergio Duque and Lesley Baker for the volumetric modulated arc therapy plan of the patient shown in Box 5.

References

Linked content

  • MJA InSight: Radiotherapy for breast cancer: a fast-evolving field

  • MJA Podcast: Prof John Boyages

Provenance: Commissioned; externally peer reviewed.

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