Treatment of Bilateral Breast Cancer and Regional Nodes Using an Opposed Lateral Beam Arrangement

Introduction

Synchronous bilateral breast cancer (BBC), defined as having a bilateral breast cancer diagnosis within 3 months of the primary, has an estimated incidence of 1–3% among newly diagnosed breast cancer patients (1–3). BBC has a rising incidence since the 1970’s, largely due to the widespread adoption of bilateral mammography as part of the work-up for newly diagnosed unilateral breast cancer (UBC), leading to the early detection of contralateral disease (4). BBC patients have higher rates of distant metastatic disease and worse disease-specific survival when compared to patients with UBC. However, local-regional control is equivalent for BBC and UBC (5). For this reason, breast-conserving therapy (BCT) followed by adjuvant radiation is offered to patients with early stage BBC as an option, along with bilateral mastectomy without radiation (6). For BBC patients undergoing radiation after BCT, treatment of the bilateral breasts is conventionally done using a 3D-conformal technique using opposed tangential photon fields (7). Others have reported using VMAT or helical tomotherapy to treat the bilateral breasts, showing a possible reduction in dose to the lung and heart utilizing this approach (8–10). However, when patients require treatment of the bilateral breasts along with regional nodal irradiation (coverage of internal mammary chain, supraclavicular, and axillary levels I-III), there is no consensus of the optimal radiation treatment technique. Given recent publications demonstrating a disease-free survival advantage with radiation targets including all of the undissected nodal basins in select patients with high risk early stage breast cancer (11–13), we anticipate an increasing clinical need to customize radiation beam arrangements to comprehensively treat areas at risk for women with BBC that fit this categorization.

Case Report

This is a case is of a 53-year-old female who had a right breast lesion detected through a routine screening mammogram at an outside facility. She underwent a confirmatory right breast ultrasound which showed a hypoechoic lesion at 10 o’clock measuring 2.2 cm in largest dimension, which was biopsied and revealed invasive ductal carcinoma, grade 1, ER+, PR+, and Her-2/Neu non-amplified. The patient then underwent a bilateral breast MRI which showed the right breast upper-outer quadrant lesion, along with a lesion in her left breast at 1 o’clock, measuring 5 cm in largest dimension. This left breast lesion was biopsied and pathology returned as invasive lobular carcinoma, grade 2, ER+, PR-, Her-2/Neu non-amplified. She then presented to our institution for consultation and evaluation of treatment options.

The patient requested breast conservation, and underwent a needle-localized bilateral segmental mastectomy with sentinel lymph node biopsy. The final pathologic stage for her right-sided upper-outer quadrant lesion was T2 N1a M0, unifocal, measuring 4.8 cm in largest dimension. 1 out of 4 sentinel lymph nodes were positive for carcinoma, measuring 0.7 cm, with extracapsular extension (ECE) noted. There was no lymphovascular space invasion (LVSI) seen. For her left-sided upper-outer quadrant lesion, the final pathologic stage was T3 N0 M0, multifocal, measuring 6.0 cm in largest dimension, with LVSI noted. Zero of 6 sentinel lymph nodes examined were positive for carcinoma. She had final negative margins on her right side, and close margins (<2mm) on her left side. The patient received adjuvant systemic therapy including four cycles of paclitaxel and 4 cycles of dose-dense doxorubicin and cyclophosphamide chemotherapy.

We used a nomogram to predict this patient’s risk of additional positive non-sentinel lymph nodes for her right-sided lesion, and it was estimated to be 34% (14). We discussed with the patient that she was a borderline candidate for requiring regional nodal irradiation (RNI) for each of her breast cancers. We weighed her risk of additional lymph node involvement for the right and left breast cancers, and the disease free survival benefit of RNI as well as the side effects associated with RNI (12, 13). She elected to pursue radiation to the bilateral breasts and undissected lymphatics.

Radiation Treatment Planning

The patient underwent a CT simulation using respiratory gating in the supine position. She was immobilized with an upper custom Vac-Lok® body mold, with both of her arms abducted. Wires were used to mark her superior and inferior breast clinical treatment borders. Images were imported into a treatment planning system (Pinnacle). Three differing treatment plans were generated for evaluation (Figures 1–2): 1) Conventional plan consisting of bilateral opposed medial and lateral tangents, a right and left anterior-posterior (AP) oblique supraclavicular field, and bilateral upper and lower internal mammary chain (IMC) electron fields; 2) Opposed lateral plan consisting of right and left lateral beams matched superiorly to the right and left AP oblique supraclavicular fields, with a right and left upper and lower electron patch to cover the lateral aspect of the breasts and an anterior appositional photon supplement to the bilateral internal mammary chains; 3) a 28-field IMRT plan. We contoured the bilateral breasts, right and left IMC, right and left supraclavicular nodal regions, right and left undissected axillary lymph nodes, and key organs at risk (OARs) including her heart and lungs.

Figure 1.

3D skin rendering of the patient and representative beams which were used to generate the opposed lateral treatment plan. The orange and sky blue colors represent the right and left lateral fields, respectively. The dark blue field is the anterior IMC supplement, and the purple and maroon beams are the right and left electron patches treating the lateral breasts and undissected axilla. The yellow and green fields represent the right and left AP oblique supraclavicular fields, respectively, which were matched inferiorly to the opposed lateral beams.

Figure 2.

Representative CT scan axial slices at the same plane for the conventional plan (A), opposed lateral plan (B), and IMRT plan (C). In the conventional plan (A), “cold triangles” (blue arrows) can be seen at the junction of the opposed tangential (red-medial, green-lateral) fields with the AP electron IMC field (yellow). The orange and sky blue beams represent the right and left lateral fields, respectively, in the opposed lateral plan (B). The dark blue beam is the anterior IMC supplement, and the purple and maroon beams are the right and left electron patches, respectively. Shown in yellow colorwash are the bilateral breast contours.

Field-in-field techniques were used for the opposed lateral and supraclavicular fields to reduce hot spots and the brachial plexus dose. For the right and left electron patches covering the lateral aspect of the breasts, 16 MeV electrons were used for the upper patches and 12MeV for the lower. All field junctions were single treated, with the exception of the left electron patches, which were double treated with the left opposed lateral photon beam. This was done to ensure adequate left breast tumor bed coverage, as the left tumor bed extended into the penumbra edge of the lateral photon field. During planning, we noticed the IMC lymph nodes were slightly under dosed posteriorly, so an AP 6 MV photon supplement was added. A photon supplement was chosen over an electron supplement to avoid additional unnecessary skin dose. A slight couch kick of 356 and 4 degrees was used for the right and left lateral photon beams, respectively, to make a non-divergent border with the supraclavicular fields. The right and left lateral electron patch beam angles were chosen to obtain optimal coverage of the breast and axilla, while avoiding a cold triangle and potential collisions with the cone and Vac-Lok® during setup. Also, extended electron SSDs were required to avoid any collisions during setup. When using the photon opposed laterals approach, two separate isocenters were required to avoid the machine from colliding with the patient. Daily setup, imaging, and complexity from treating with multiple fields and isocenters required additional time on the treatment table.

We compared the three treatment plans to evaluate which one would offer the best coverage of our target areas while at the same time minimizing dose to OARs. The conventional plan had inadequate coverage of her breasts, largely due to the “cold triangles” that occurred when matching opposed tangential beams with the appositional upper and lower bilateral electron IMC fields (Figure 2). Although coverage of the breasts was similar for the IMRT and opposed lateral plan, the mean dose to the heart and V20 for the bilateral lungs was found to be higher in the IMRT plan (Table 1, Figure 3–4), due to increased integral dose. Conversely, the opposed lateral plan had higher maximum point doses for our target structures and OARs. We weighed the pros and cons of each approach, and opted to treat our patient with the opposed lateral plan to a total dose of 50 Gy in 25 fractions to her bilateral breasts, and bilateral undissected regional nodes. Field borders were drawn in at the time of her first treatment to help with daily set-up, along with weekly kV imaging. This was followed by a 14 Gy tumor bed boost in 7 fractions using an electron field on the left side (due to close margins) and a 10 Gy tumor bed boost in 5 fractions on the right side. The patient completed her treatment without any breaks and, had grade 1 dermatitis, fatigue, and hyperpigmentation that became noticeable a few weeks into treatment (Figure 5). She was started on anastrozole at the end of her treatment. We plan to see her back in clinic in 6 months for a physical examination and repeat bilateral mammogram.

Table 1.

V80, V90, and V95 represent the percent of the volume of the target structures receiving 80%, 90%, and 95% of the prescribed dose of 50 Gy. V20 represents the percentage of the bilateral lungs receiving an absolute dose of 20 Gy or higher. Mean and maximum doses are listed in cGy.

	Conventional				Opposed Lateral				IMRT
Target Structures	V80	V90	V95	Max	V80	V90	V95	Max	V80	V90	V95	Max
Bilateral Breasts		92.8	88.6	8282.6		97.4	94.3	8042.4		99	96.1	5994.3
Bilateral SCV		98.3	76.1	5416.0		100	99.3	6507.2		93.6	82.1	5213.0
Bilateral IMC	100	100		5476.4	100	100		5233.2	100	99		4986.0
Bilateral Axillae		99.8	99.4	5870.6		99.7	98.5	7616.9		99.6	75.3	5630.7
Organs at Risk	V20	Mean		Max	V20	Mean		Max	V20	Mean		Max
Bilateral Lungs	19.5			5690.0	27.3			6539.2	37.5			5516.4
Heart		734.2		5133.8		439.5		4513.7		871.6		4268.9

Figure 3.

Dose volume histogram illustrating absolute doses for the conventional (thick solid line), opposed lateral (dashed line), and IMRT (thin solid line) treatment plans. The orange, blue, and pink curves represent coverage of the bilateral breasts, bilateral lungs, and heart contours, respectively.

Figure 4.

Representative CT scan axial slices at the same plane for the opposed lateral plan (A) and IMRT plan (B), with the bilateral breast contour in yellow colorwash. The 100%, 95%, 90%, 50%, and 20% isodose lines are shown. The IMRT plan had higher low dose exposure to both the heart and lungs in comparison to the opposed lateral plan.

Figure 5.

Images obtained at 2 weeks into treatment (left image) and at the end of treatment (right image). Towards the end of treatment, mild grade 1 hyperpigmentation and dermatitis can be noted over the treated bilateral breasts.

In our patient, the opposed lateral plan offered a novel approach to treat the bilateral breasts and regional nodes with an overall reduced dose to the heart and lungs compared to the IMRT plan, and with better target coverage than the conventional plan. One downside to this approach in comparison to the IMRT plan was the complexity requiring a mix of photons and electrons and the overall total number of treatment fields and isocenters. During CT simulation, one should be mindful of trying to reduce the bulkiness of the Vac-Lok® in order for the electron patches to have clearance during setup. Also, one should consider the horizontal separation of the patient for the opposed laterals set-up. The larger the separation, the hotter the plan, especially if 6 MV photons are required to treat superficial tumor beds. During planning, one should the mindful of placing isocenters appropriately to avoid any collisions during treatment.

In conclusion, we recommend tailoring treatment of BBC patients on a case-by-case basis. In cases where regional nodes do not need to be treated, opposed tangential beam plans, as well as IMRT and VMAT techniques have been shown to work effectively with overall low lung and heart mean dose, and should be considered along with conventional opposed-tangential beam plans. However, in cases where the bilateral breasts and regional nodes are both needing treatment, comparative plans should be generated to see which offers optimal target coverage along with normal tissue sparing.