Radiation Oncology Breast Cancer

Radiation’s Role for Breast Cancer Nodes: Assessing Risk

Radiation has an essential role in breast cancer, complementing surgery to prevent recurrences and improve survival. To determine when radiation helps treat lymph nodes in breast cancer, we need to carefully interpret surgical findings and accurately stage breast cancer to best understand the risk of lymph node involvement.

The NCIC and EORTC trials showed that treating the regional lymph nodes comprehensively can decrease recurrences, and pooled together they demonstrate improved overall survival.1 But in these studies, all the lymph node areas were treated (Fig. 1). Making decisions on treating them individually or comprehensively can be complicated.

Fig. 1: Budach et al, Radiat Oncol 2015

Radiation oncologists have to determine the risk of clinically meaningful disease in the nodes based upon the many pathologic features from the primary tumor and overall stage. Let’s take a look first at the nodes themselves and then some of the factors that play a role in deciding to treat them (Fig. 2).

Fig. 2: Cancer.Net (author’s annotation)

Internal mammary nodes (red) are not standardly sampled but some trials included in extended surgeries, so we have older studies with information. More modern studies really look only at biopsy rather than full dissection, which didn’t improve survival.2 The risk clearly seems related to medial location and axillary nodal status.3

Chance of Internal Mammary Involvement (T1-2)

Axillary LN –

Axillary LN+

Outer/Lateral Breast

4%

17%

Inner/Medial Breast

11%

32%

Table 1: Lacour et al, Cancer 1976

Supraclavicular/infraclavicular nodes (blue) are not dissected or sampled at all; we know the least about patterns of spread because they aren’t sampled unless suspected already or recurrences occur. Decisions are usually made to treat based upon the axillary lymph nodes.

Axillary nodes (green) are the most understood, based upon axillary dissections and more recently using sentinel lymph node biopsy to limit the need for larger surgeries.  We have a lot of good surgical data to estimate the risk of involvement.

Recent studies suggest sentinel lymph node biopsy may be enough axillary surgery for clinically node negative breast cancer patients who have microscopic node involvement with otherwise favorable features.4,5 But as we do less surgery, radiation oncologists also have less information to base decisions upon and may be asked to irradiate more often.

Here are all the areas treated with comprehensive nodal irradiation (Fig. 3).

Fig. 3: Budach et al, Radiat Oncol 2015

Maybe we can spare some nodes if we know that the risk of clinically meaningful disease is low.  The NCIC and EORTC trials suggest that ‘high risk’ patients with T2 (2.1-5cm) tumors, medial/central location based upon axillary dissections may benefit the most. Many debate what degree of lymph node involvement warrants adding nodal radiation. Careful selection will be particularly important now since we increasingly offer sentinel lymph node biopsy rather than axillary node dissection for clinically node negative breast cancer.

Predictive tools can help decide whether nodal radiation. For women who undergo mastectomy and aren’t already getting radiation after a breast-preserving surgery, it can be a more challenging decision especially if many women are choosing up-front reconstruction before lymph node status is really known.  So here are some currently available tools to assess risk of nodal involvement.

For the patients with a positive axillary sentinel node biopsy, multiple institutions have models to estimate the chance of more positive nodes, which may tilt toward the decision to irradiate. The two most tested and validated are from Memorial Sloan-Kettering and MD Anderson.6,7 Some patients may not need radiation with a positive sentinel node, but the ACOSOG Z0011 trial was a carefully selected group of patients, and it had a lot of variability in radiation fields that could have affected failure rates.8

Supraclavicular nodes are harder since we don’t have surgical series giving us accurate estimates. Knowing there is more than one positive lymph node may be enough for some, based upon the nomograms above. If the bar is set higher, having at least four positive nodes to treat the supraclavicular fossa, then Massachusetts General Hospital has a useful nomogram.9  If you were to follow the NCIC MA.20 and EORTC trials though, arguably this cutoff isn’t needed because the 85% of the MA.20 patients and 43% of the EORTC patients had 1-3 nodes involved.

Many radiation oncologists are hesitant about the internal mammary nodes (IMNs).  A small French trial was negative in treating the IMNs. But a recent large Danish cohort study showed a survival benefit when the IMNs received radiation just by treating them for right sided breast cancers but not left-sided to minimize cardiac risk.10 In some anatomic areas, the survival differences were statistically and clinically significant:

Laterality

#+Axillary LNs

8-Year Overall Survival (%)

Hazard Ratio (CI)

IMN RT

No IMN RT

All

75.9

72.2

0.82 (0.72-0.94)

Lateral

1-3

82.9

85.7

1.13 (0.84-1.51)

≥ 4

68.0

58.3

0.71 (0.57-0.89)

Medial/Central

1-3

83.2

78.8

0.80 (0.58-1.10)

≥ 4

61.9

53.8

0.81 (0.61-1.06)

Table 2: Thorsen et al.

We need better tools to estimate the potential reward of improving cure rates by treating the lymph nodes. The estimates above help but aren’t enough. Finding lymph node involvement, or suspecting it, doesn’t mean radiation is always needed. That decision also depends upon the biology of breast cancer and the effectiveness of systemic treatments, which will be the next topic we cover.

This post was originally published on ASCO Connection.

References

  1. Budach W, Bölke E, Kammers K, et al. Adjuvant radiation therapy of regional nodes in breast cancer – a meta-analysis of randomized trials – an update. Radiat Oncol. 2015;10:258.
  2. Lacour J, Le M, Caceres E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection. Ten-year update of an international cooperative trial in breast cancer. Cancer. 1983;51:1941-3.
  3. Lacour J, Bucalossi P, Cacers E, et al. Radical mastectomy versus radical mastectomy plus internal mammary dissection. Five-year results of an international cooperative study. Cancer. 1976;37:206-14.
  4. Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC-10981-22023 AMAROS): a randomized, multicentre, open-label, phase 3 noninferiority trial. Lancet Oncol.2014;15:1303-10.
  5. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis. JAMA. 2011;305:569-75.
  6. Van Zee KJ, Manasseh DM, Bevilaqua JL, et al. A nomogram for predicting the likelihood of additional nodal metastases in breast cancer patients with a positive sentinel node biopsy. Ann Surg Oncol. 2003;10:1140-51.
  7. Mittendorf EA, Hunt KK, Boughey JC, et al. Incorporation of sentinel lymph node metastasis size into a nomogram predicting nonsentinel lymph node involvement in breast cancer patients with a positive sentinel lymph node. Ann Surg. 2012;255:109-15.
  8. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z011 (Alliance) trial. J Clin Oncol. 2014;32:3600-6.
  9. Katz A, Smith BL, Golshan M, et al. Nomogram for the prediction of having four or more positive involved nodes for sentinel lymph node-positive breast cancer. J Clin Oncol. 2008;26:2093-8.
  10. Thorsen LB, Offersen BV, Danno et al. DBCG-IMN: a population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol. 2016;34:314-20.