8.5 References
Chapter Ⅷ Radiation Therapy for Breast Cancer
8.1 Indications and Principles of Breast Cancer Radiotherapy
8.1.1 Breast Anatomy
Localized regional radiotherapy for breast cancer generally requires irradiation of the breast/thoracic wall，axillary fossa，supraclavicular and internal mammary lymphatic drainage areas.The design of the irradiation field requires not only reference to surgical methods，tumor staging，tumor characteristics and failure modes，but also to each patient anatomy.Understanding the anatomy of the breast and lymphatic drainage areas helps to properly map the target area and perform radiotherapy.
The mammary gland is attached to the surface of the pectoralis major fascia，mostly between the 2nd and 6th anterior ribs，the inner boundary is the sternal border，and the outside reaches the anterior or medial line.The outer upper pole can extend to the armpit to form the appendix of the breast.The inner side of the breast is 2/3 on the surface of the pectoralis major and the outer third is on the surface of the anterior serratus.A small part of the breast tissue can exceed the above range，reach the lower edge of the clavicle，and release the anterior sheath of the rectus abdominis，which reaches the midline of the body and reaches the leading edge of the latissimus dorsi.The junction of the lower edge of the breast and the surface of the trunk is called the underlying breast fold.The outer upper quadrant of the breast has the largest glandular tissue and is the most common site of breast cancer.
The mammary gland is located between the superficial and deep layers of the subcutaneous superficial fascia.The superficial layer of the superficial fascia is located deep in the dermis and is a fat-rich connective tissue；the deep layer of the superficial fascia is located deep in the mammary gland and is connected with the loose connective tissue between the superficial layers of the pectoralis major fascia.The superficial fascia extends into the mammary gland to form a fibrous septum（called the breast suspensory ligament or Cooper ligament），one end connected to the skin and one end connected to the pectoral fascia，which supports the mammary gland.The superficial and deep layers of the superficial fascia and the mammary gland enclosed in it are the main resection areas of radical mastectomy，and are also the main content of total breast irradiation after breast conserving surgery.The mammary gland consistsof a ductal glandular tissue（substantial），fibrous connective tissue（interstitial）surrounding the glandular tissue，and adipose tissue.The mammary gland is composed of the lactiferous duct，the mammary gland，and the acinus.Adult breasts have 1520 glandular lobes，arranged radially around the nipple.The lymphatic system of the breast includes lymphatic vessels in the breast and lymphatic vessels and regional lymph nodes from the breast.The lymphatic vessels in the breast are composed of the capillary lymphatic network of the skin and mammary gland.The lymphatic vessels of the breast skin are located in the dermis，with shallow and deep layers of capillary lymphatic network.The superficial lymphatic network has extensive communication with the superficial lymphatic network of the surrounding skin.When the tumor invades the blocked lymphatics，the cancer cells It can be reversed through the superficial lymphatic network，invading the contralateral breast，contralateral axillary lymph nodes or chest and abdomen back skin.The mammary gland is mainly drained to the axillary，internal milk，and supraclavicular lymph nodes，and can also be drained to the intermuscular lymph nodes（Rotter's lymph nodes）.
The armpit is a fat，connective tissue cavity.The inner wall of the sacral cavity is the anterior serratus muscle.The anterior wall is the chest and small muscles.The posterior wall is the muscle and fascia of the subscapular region.The axillary lymph nodes are arranged along the axillary nerve vessels.There are two methods for grouping according to the location，the extent of lymphatic storage，and clinical needs：1.anatomical grouping（pre-group，posterior group，lateral group，central group，and tip group）.The anterior group receives the mammary gland lymph；the posterior group receives the lymph in the back，scapular and posterior wall；the lateral group receives the lymph of the upper limb；the central group receives the anterior，posterior，lateral，and partial lymph nodes that directly receive the mammary gland；Subclavian lymph nodes，（arranged along the proximal end of the iliac vein）the anterior，posterior，lateral，central and intermuscular lymph nodes of the axilla，and the lymph nodes in the upper part of the breast；2.clinical grouping（level Ⅰ，level Ⅱ and levelⅢ），level Ⅰ（low armpit）is located outside the pectoralis minor；level Ⅱ（median armpit）is located deep in the pectoralis minor（including the intermuscular lymph nodes）；level Ⅲ（the crest or subclavian）is located inside the pectoralis minor，that is，the cluster of lymph nodes（Figure 8-01）.Axillary lymph node metastasis in breast cancer is mostly from level i to level Ⅱ，and then to level Ⅲ，jump metastasis is rare，at about 3%-3.8%.
The internal mammary lymph nodes are located in the sternal intercostal space and are arranged along the internal thoracic arteriovenous layer of the extrapleural fat layer，mainly in the 1～3 intercostal space（Fig.8-02）.The inner mammary lymph nodes and their lymphatic vessels are also commonly referred to as the inner breast lymphoid chain.The output lymphatic vessels of the internal mammary lymph nodes were injected into the supraclavicular lymph nodes，or the right lymphatic duct was injected into the right side，and the thoracic duct was injected into the left side or directly into the jugular vein.
The supraclavicular lymph nodes contain most of the lymphatic drainage of the apex group and the internal mammary lymph nodes.They are located in the connective tissue above the clavicle and deep in the platysma.The deep side is the scalene muscle，the inner boundary is the internal jugular vein，and the outside is the trapezius muscle.The upper boundary is the level of the ring membrane and the lower boundary is the subclavian vein.The output lymphatic vessels of the supraclavicular lymph nodes andthe deep cervical lymph node output tube synthesize the neck stem，sink the human thoracic duct or the right lymphatic duct，or directly inject into the jugular vein.The vicinity of the junction of the internal jugular vein and the subclavian vein is the predilection site for lymph node metastasis（Fig.8-03）.
Figure 8-01 CT shows right Ⅰ-Ⅲ horizontal axillary lymph node metastasis
Figure 8-02 CT shows left breast lymph node metastasis
Figure 8-03 CT shows right supraclavicular lymph node metastasis
8.1.2 Radiotherapy for Intraductal Carcinoma of the Breast
Patients with intraductal carcinoma of the breast have a higher rate of recurrence of ipsilateral breast tumors after breast-conserving surgery.Among them，50%of recurrent tumors are intraductal carcinoma and 50%are invasive carcinoma.Four randomized clinical studies have found that after intraductal cancer breast conserving surgery，radiotherapy has reduced the recurrence rate of ipsilateral breast tumors by half compared with non-radiotherapy，including reducing the recurrence rate of intraductal and invasive carcinomas，but did not improve overall survival.In all four studies，the whole breast was irradiated with a total dose of 50 Gy/5 weeks（the total dose of some patients in the SweDCIS study［1］was 54 Gy，with a 2 week rest）.In the NSABP B-17［2］and EORTO-10853 studies［3，4］，9%and 5%of patients in the radiotherapy group received a tumor bed supplement of 10 Gy，and no tumor bed replenishment was found in the SweDCIS and UKCCCR studies［5，6］.A meta-analysis of 3729 patients in the above 4 randomized studies showed that radiotherapy significantly reduced the recurrence rate of ipsilateral breast tumors.The 10-year ipsilateral breast tumor recurrence rates in the radiotherapy and non-radiation groups were 12.9%and 28.1%，respectively（P＜0.0000）.No subgroups were found who could not benefit from radiotherapy，including age＜50 and≥50，newly diagnosed tumors were detected by mammography or clinical symptoms，tumors were single or multifocal，tumors were low，medium or high graded.Local or resection of the operation，negative or positive margin，and the use of tamoxifen，postoperative breast-conserving radiotherapy can significantly reduce the recurrence rate of ipsilateral breast tumors.Even for patients with low grade，tumor size 1～20 mm，and negative margin，postoperative breast-conserving radiotherapy significantly reduced the recurrence rate of ipsilateral breast tumors in 10 years（30.1%and 12.1%，P=0.002）.Older patients benefit from the same local control in radiotherapy.The 10-year ipsilateral breast tumor recurrence rate of≥50 years old patients with radiotherapy and non-radiation was 10.8%and 27.8%，and the＜50-year-old patient had radiotherapy and 10 years of ipsilateral radiotherapy.The recurrence rate of breast tumors was 18.5%and 29.1%.Radiotherapy did not significantly reduce breast cancer mortality or total mortality compared with non-radiotherapy，nor did it significantly increase non-breast cancer mortality or heart disease mortality［7］.
The mortality rate of intraductal carcinoma of the breast is extremely low.NSABP B-17 and B-24 studies have shown that breast cancer mortality in the 15-year period is only 2.3%-4.7%.The recurrence of ipsilateral breast invasive carcinoma continued to increase after 15 years of surgery，and the recurrence of invasive cancer increased the risk of breast cancer death（HR=7.06）and total mortality（HR=1.75）.Radiotherapy significantly reduced the risk of recurrence of ipsilateral breast invasive carcinoma.The recurrence rate of ipsilateral invasive carcinoma in patients with simple breast-conserving surgery and postoperative radiotherapy was 19.4%and 8.9%，respectively.The recurrence of intraductal cancer continued to increase within 5 years after surgery，and the recurrence rate reached the platform after 5 years，but the recurrence of intraductal cancer did not affect the survival of the patient.The study found that age＜65，positive margin/unknown（vs margin negative），clinical detection（vs only mammography）is a high risk factor for invasive cancer recurrence［8］.The 15-year follow-up of the EORTC-10853 study also showed that the risk of breast cancer death in patients with ipsilateral breastinvasive cancer recurrence was 17 times higher than in patients without recurrence or intraductal cancer recurrence［4］.Solin et al reported that in the E5194 study，patients with non-radiotherapy after intraductal cancer breast-conserving surgery，12 gene scores can identify low-，medium-，and high-risk patients with recurrence.The 10-year local recurrence rates were 10.6%，26.7%，and 25.9%，respectively.The recurrence rate of invasive cancer was 3.7%，12.3%，and 19.2%（P≤0.006）［9］.Combined with clinical pathological factors and molecular markers，selection of high-risk patients with recurrence，especially high-risk patients with invasive cancer recurrence，can maximize the benefit of radiotherapy.
Radiotherapy after breast-conserving surgery in patients with intraductal cancer is routinely segmented.Intraductal cancer patients with breast cancer after radiotherapy need to irradiate the whole breast 50Gy/25F，without the need to prevent lymph nodes in the irradiated area.There is no randomized evidence for the need for tumor bed replenishment after total breast irradiation.Irradiation is based on the extrapolation of the tumor bed after the retention of the breast in invasive cancer.patients is more extrapolated than the non-compensatory.Irradiation can further reduce the local recurrence rate.Retrospective studies have shown that intraductal carcinoma bed replenishment does not generally improve localization or survival，but young patients may benefit from tumor bed replenishment.At present，TROC07.01 and EORTC22085 are conducting phase Ⅲ randomized clinical trials on the need for postoperative radiotherapy for intraductal cancer to maintain postoperative radiotherapy.The results will provide a basis for treatment decisions.
There are few studies on partial breast irradiation after breast conserving surgery in patients with intraductal carcinoma of the breast.ASTRO partial breast irradiation consensus suggests that patients with intraductal cancer should be cautious with partial breast irradiation（tumor≤3cm）or unsuitable to do it（tumor＞3cm）.
8.1.3 Radiotherapy After Breast Conserving Surgery on Early Invasive Breast Conler
Radiotherapy after breast-conserving breast cancer can significantly reduce the local recurrence rate of ipsilateral breast tumors.Meta-analysis showed that radiotherapy can also reduce distant metastasis rate and improve overall survival rate.The 10-year failure rate（local or distant metastasis）of patients with radiotherapy and non-radiation is 19.3%and 35%，respectively（p＜0.00001），15 years.Breast cancer mortality was 21.4%and 25.2%，respectively（p=0.0000），and the 15-year total mortality was 34.6%and 37.6%，respectively（p=0.03）.
Breast-conserving surgery patients，including various types of invasive cancer，whether the axillary lymph node is negative or positive，should generally be treated with postoperative radiotherapy.For example，in the NSABP B-06 randomized study，the 20-year local recurrence rates of patients after and after breast-conserving surgery were 14.3%and 39.2%，respectively.Patients with negative axillary lymph nodes and positive patients can benefit from radiotherapy.Patients with axillary lymph node-negative，radiotherapy and non-radiotherapy the recurrence rates of them were 17%and 36.2%，respectively；the 20-year local recurrence rates of patients with axillary lymph node-negative，radiotherapy and non-radiation were 8.8%and 44.2%，respectively.
Based on the current effective systemic therapy，combined with clinical low-risk factors and molecular typing，a group of patients without radiotherapy can be screened.CALGB9343 study enrolled patients with age≥70，T1N0M0（2/3 is cNO），surgical margin negative and ER-positive breast-conserving surgery，randomized to tamoxifen or postoperative radiotherapy+tamoxifen，5-year local recurrence rate of tamoxifen was 4%，the postoperative radiotherapy+tamoxifen group was 1%（P＜0.000）［10］.The 10-year local recurrence rate was 10%in the tamoxifen group alone，and the postoperative radiotherapy+tamoxifen group was 2%（P＜0.0001）.There was no difference in overall survival and breast cancer-specific survival（up to 98%and 97%）［11］.
After breast-conserving surgery，the patient underwent routine breast irradiation，and the conventional breast tangential field irradiation dose was 45-50 Gy，5 weeks，1 time/day，1.8-2 Gy/time.After the whole breast irradiation，the tumor bed should be supplemented with radiation.Clinically，if the surgical margin is negative，the tumor bed dose is 10-16Gy；if the surgical margin is positive，the tumor bed dose is 15-20Gy，which is routinely divided.The range of the tumor bed replenishment irradiation is determined according to the metal mark placed around the intraoperative tumor bed，the seroma after breast surgery and the postoperative change range of the CT image；the patient who has not placed the metal mark during the operation can refer to the physical examination and surgical scar location.
Whether it is necessary to prevent lymph nodes in the breast cancer after breast-conserving surgery，and which regional lymph nodes are irradiated，mainly refer to the risk of subclinical involvement of regional lymph nodes at the time of initial diagnosis，the risk of postoperative lymph node recurrence，the efficiency of radiotherapy，the toxicity of radiotherapy，and the rescue after recurrence.The success rate of treatment and the effectiveness of systemic treatment to control distant subclinical lesions.In general，patients with pathologically negative axillary lymph nodes（axillary dissection or sentinel lymph node biopsy）do not require regional lymph node prophylaxis；patients with axillary lymph node metastasis≥4 need to prevent regional lymph nodes；patients with 1～3 axillary lymph node metastases need Patients with high risk factors are selected to prevent lymph nodes in the irradiated area.
The 2016 NCCN guidelines recommend that total breast radiotherapy be routinely divided，with a total dose of 46-50 Gy/（2Gy·23～25F）or a large division of 40-42.56Gy/15～16F（preferably large）.The tumor bed of patients with high recurrence risk is 10-16Gy/4～8F.According to the results of its own clinical research，the Cancer Hospital of the Medical College has a total breast segmentation of 43.5 Gy/（2.9 Gy·15F）and a tumor bed supplement of 8.7 Gy/（2.9 Gy·3F）.Large-segment radiotherapy that increases the single-dose dose and reduces the number of radiotherapy can shorten the radiotherapy cycle，enable patients to complete radiotherapy as soon as possible，reduce the number of patients returning to the hospital or shorten the hospital stay，and save medical resources.It is currently believed that breast cancer has a lower αβ value.From a radiobiological perspective，breast cancer large-segment radiotherapy can not increase the patient's late radiotherapy complications on the basis of ensuring efficacy.
The majority of patients with ipsilateral breast recurrence after breast-conserving surgery（about 80%）are located around the surgical incision.The tumor recurrence rate in other quadrants is about 15%，which is similar to the incidence of contralateral breast cancer.It may not be recurrence.Secondprimary cancer.Based on this，the clinical study of partial breast irradiation after breast conserving surgery was carried out abroad，and the scope of radiotherapy only included the area of the breast tumor bed.Part of the breast irradiation target area is reduced，and the irradiation method of accelerating the large segmentation can be adopted.The radiotherapy is completed in one week without causing a serious acute or late radiotherapy reaction.Accelerated partial breast irradiation（PBI）can reduce the dose of the heart，lung，chest wall and contralateral breast，but also reduce the dose of the ipsilateral mammary gland outside the tumor bed，which may improve the cosmetic effect of the breast and also cause recurrence after breast conserving surgery.It is possible for patients to undergo breast-conserving surgery and radiotherapy again.The PBI study was enrolled in low-risk patients.According to the long-term follow-up results of some phase Ⅱ clinical studies，the 2014 ASTRO PBI Consensus proposed the following appropriate conditions：age≥60，no BRCA 1/2 gene mutation，primary tumor maximum diameter≤2 cm，at least 2mm negative margin，single lesion center，no vascular tumor thrombus，ER negative，pathological invasive ductal carcinoma or other good type，pathology is not invasive lobular carcinoma，EC negative，axillary lymph node negative，no new adjuvant therapy.For the above patients，PBI may achieve the same efficacy as total breast irradiation.
8.1.4 Radiotherapy after Total Mastectomy on Early Invasive Breast Cancer
Early breast cancer can be performed with total mastectomy，and axillary treatment with axillary dissection and sentinel lymph node biopsy.Sentinel lymph node biopsy is indicated for patients with negative axillary lymph nodes.If the sentinel node is negative，no further axillary dissection is required；if the sentinel node is positive，further axillary dissection is required.However，if the lymph node metastasis lesions are small，it is still controversial whether it is necessary to clean.2016 American Society of Radiation Oncology guidelines：if doctors and patients choose not to have axillary dissection，regardless of the outcome of further axillary cleansing，there is enough information to support the patient's need for postoperative radiotherapy，you can choose radiotherapy；if not enough Information support patients need postoperative radiotherapy，and axillary cleansing is recommended.
The chest wall and the upper and lower lymphatic drainage area of the clavicle are the most common recurrence sites in patients after total mastectomy.Radiotherapy is generally used to irradiate these two parts；whether the inner breast area needs to prevent radiation has been controversial.The preventive dose of the chest wall and regional lymph nodes was 45-50 Gy，1.8-2 Gy，once daily，5 weeks.There are no randomized clinical trials of large-segment radiotherapy after modified radical mastectomy for breast cancer.
8.1.5 Radiotherapy for Locally Advanced Breast Cancer
Local staged breast cancer refers to the tumor burden in the breast and regional lymphatic drainage area，but there is no distant organ metastasis，mostly in the clinical stage Ⅲ，ie T3（breast tumor＞5cm）with lymph node metastasis，T lesion，or N2，N3 lesions.Clinical manifestations include breast skin ulcers，edema，satellite nodules，tumor invasion of the chest wall，axillary lymph node fusion，internal mammary lymph node metastasis，supraclavicular and inferior lymph node metastasis.
The scope of postoperative radiotherapy for modified radical mastectomy was mainly in the chest wall and the upper and lower lymphatic drainage areas of the clavicle.The dose segmentation method was the same as the radiotherapy after radical mastectomy in early stage.For patients with supraclavicular or internal mammary lymph node metastasis at the time of initial diagnosis，the upper supraclavicular region or the inner breast region（between 1 and 3 intercostal spaces）should be irradiated with 45-50 Gy，and the original supraclavicular or internal mammary lymph node metastasis should be irradiated.If the supraclavicular or internal mammary lymph nodes disappear after chemotherapy，add 10Gy/5f；if the supraclavicular or internal mammary lymph nodes remain after chemotherapy，add 16～20Gy/8-10F.In order to reduce radiotherapy damage，try to avoid total lymph node area irradiation，which requires the patient to carry out CT examination of the corresponding site at the time of initial diagnosis，to identify the initial lymph node metastasis，to provide reference for radiotherapy to determine the supplementary irradiation range，to prevent lymph node disappear completely after chemotherapy.It is not possible to accurately locate the replenishment range.At the same time，it is emphasized that the lymphatic drainage area should be carefully evaluated at the time of initial diagnosis，and the swollen suspicious metastatic lymph nodes should be puncture for tissue examination to avoid missed diagnosis and insufficient dose of radiotherapy.
In patients with locally advanced breast cancer who are unable to undergo surgery after neoadjuvant chemotherapy，preoperative radiotherapy or radical radiotherapy may be performed.The preoperative radiotherapy dose was 50Gy，and the probability of complications was increased.At the time of radical radiotherapy，the total breast dose was 50 Gy，and then the residual lesion was irradiated with additional dose.According to the size of the residual lesion，the additional dose was 10-20 Gy.The dose in the lymphatic drainage area is 45～50y/4.5～5 weeks，then 10～20Gy is added to the enlarged lymph nodes.The skin and subcutaneous areas of locally advanced breast cancer are highly likely to be invaded by tumors.The amount of radiation in the skin and subcutaneous areas should be increased during radiotherapy.It can be solved by adding fillers daily or every other day.Due to the high dose of skin irradiation，wet skin reactions usually occur during radiotherapy，and radiotherapy can be temporarily interrupted.After 1-2 weeks of rest，additional doses of residual lesions are applied.
8.1.6 Postoperative Radiotherapy After the Neoadjuvant Chemotherapy
After modified radical mastectomy after neoadjuvant chemotherapy，radiotherapy indications can not be based only on pathological staging，but also refer to clinical staging before neoadjuvant chemotherapy，because pathological staging only represents the extent of residual disease after chemotherapy，although neoadjuvant chemotherapy can reduce tumor's period，but did not reduce the risk of local recurrence to the same level as patients with the same pathological stage but did not receive neoadjuvant chemotherapy.The MD Anderson Cancer Center conducted a retrospective clinical analysis of 150 patients undergoing neoadjuvant chemotherapy and 1031 modified radical mastectomy patients who did not receive neoadjuvant chemotherapy.All patients received no radiation therapy.The results showed that patients with neoadjuvant chemotherapy had a higher local recurrence rate［12］than patients who did not receive neoadjuvant chemotherapy in the same pathological stage.Postoperative radiotherapy for high-risk patients after modified radical mastectomy after neoadjuvant chemotherapy can significantly improve the efficacy.
8.2 Two-dimensional Radiotherapy for Breast Cancer
8.2.1 After Breast-conserving Surgery
Early breast cancer needs to be irradiated to the whole breast after breast-conserving surgery.The patient is usually supine，the upper limb of the affected side is abducted，and the breast bracket is used for fixation.The whole breast irradiation is most commonly used for two pairs of tangential fields，which are suitable for 6MV-X ray.When irradiated with higher energy X-rays，a low dose area is formed in the shallow region of the breast close to the skin，which may affect the curative effect.Early breast cancer skin infection is unlikely，and it is not necessary to add filler when irradiated with 6MV-X-ray.Otherwise，the skin volume is too high，which may cause radiation reaction of the skin and affect the cosmetic effect.Traditionally，the whole breast has been irradiated with a two-dimensional tangential field.When the mammary gland is positioned under the fluoroscopy of the simulator，the upper boundary is at the lower edge of the clavicle，the lower boundary is 2cm below the breast fold，the posterior boundary of the incision field is in the midline，and the posterior boundary of the excision is in the midline.The front boundary of the irradiation field is 1～2cm beyond the contour of the breast skin，and the thickness of the lung tissue in the field（CLD：the thickness of the lung tissue at the center axis of the field）is generally 2～3cm（Fig.8-04）.Using the body surface contour map，according to the direction，size and isocenter position of the irradiation field during positioning，the radiotherapy plan is formulated by optimizing the dose specific gravity of the inner and outer tangential fields and the degree of the wedge plate.The disadvantage of the two-dimensional plan is that the body surface contour map is only equivalent to a single-level cross-sectional CT image lacking tissue density information.Since the plan is single-level，the dose distribution does not reflect the condition of the whole breast；due to the lack of tissue density information，lung correction cannot be performed，and the selected wedge plate degree will be different from the actual situation.At present，total breast irradiation has rarely been done in two-dimensional plans.
Figure 8-04 Two-dimensional radiotherapy technique，the position of the patient's mammary tangential field positioning A（inside field and outer field boundary line）and the tangential field map B and the two-dimensional plan dose distribution map C（the bright yellow line is 95%isodose line）
The method of supplementation of the breast tumor bed can be selected by electron beam external irradiation，X-ray external irradiation，intraoperative radiotherapy and inter-tissue implantation.Among them，electron beam external irradiation is most commonly used；X-ray external irradiation is mostly used for simultaneous filling of tumor bed；intraoperative radiotherapy requires special intraoperative radiotherapy equipment；inter-tissue interplanting is invasive and requires experienced doctors to operate，currently less used in clinical practice.In the traditional two-dimensional radiotherapy application，when the external beam is applied，the irradiation range and the irradiation depth are determined according to the surgical scar，the CT/B or the B-surgery，and the surrounding metal markers.The energy is selected to be 9～12 MeV.Apatient with a metal marker placed on the surgical tumor bed can be placed 1～1.5cm outside the surgical scar and the metal mark under the perspective of the simulator；the patient without the metal mark is directly drawn on the patient's body surface，and the surgical scar is placed outside.2～3cm（Figure 8-05）.
Figure 8-05 Breast tumor bed electron line replenishment field
Note：A and B：the irradiation field formed by the metallization of the tumor bed and the surgical scar outside under the perspective of the simulator；C：the field of radiation drawn directly on the skin of the breast according to the surgical scar.
8.2.2 After Radical Surgery
Radiotherapy for breast cancer after total mastectomy can achieve good results using conventional radiotherapy techniques.The Chinese Academy of Medical Sciences Cancer Hospital used two-dimensional radiotherapy technology（single field in the supraclavicular region and single electron field in the chest wall）from 2000 to 2004 to treat 328 patients.The 5-year local recurrence rate was only 5.8%［12］.When the conventional two-dimensional technique is released，the patient's treatment position is supine，the sloping plate of the shoulder and back is 15 degrees，and the upper limb of the affected side is abducted，so that the irradiation area is fully exposed and flattened.The upper boundary of the chest wall is the level of the lower edge of the clavicle.The lower boundary is equivalent to the 2cm level of the contralateral breast fold.The inner boundary is the midline of the body，and the outside is the midline or the posterior line.The irradiation field needs to cover all surgical scars，and does not require a full drainage port.The chest wall can be used with an electronic wire field，or a 6MVx line field.Regardless of the technique used，the chest wall needs to be filled with a filler for 20 to 30 Gy to increase the surface dose of the skin.If the skin.of the breast is invaded，increase the dose of the filler to 40 Gy.The thickness of the chest wall after breast cancer surgery is generally between 1.5-2cm，the energy of the electron beam is 6MeV，and the thickness of the filler is 0.5cm.Electron beam irradiation is suitable for patients with flat and thin chest wall（＜3cm）.For patients with thick chest wall，X-ray tangential field irradiation should be used.X-ray energy should be 6MV，and the thickness of filler should be 0.3～0.5cm.The upper boundary of the irradiation field in the supraclavicular region is at the level of the ring membrane，the lower boundary is at the lower edge of the clavicular head，and the inner boundary is at the midline of the body and the healthy side of the sternocleidomastoid muscle.The outside is at the inner edge of the humeral head.The supraclavicular lymphatic drainage area can be mixed with X-rays，or X-rays and electron lines.The single front field is used，and the angle of the rack is 10～15°.The prescribed dose is given 3 cm below the center of the irradiation field.At the same time，when the chest wall and the ipsilateral supraclavicular lymphatic drainage area are irradiated，when the chest wall is illuminated by electron beam，the irradiation field junction is collinear（Fig.8-06）；when the chest wall is irradiated with the tangential field，the chest wall tangential field and the clavicle upper field should be half-field.Irradiation technology is connected.On the basis of the chest wall and the supraclavicular field，when the axillary lymphatic drainage area needs to be irradiated，the conventional two-dimensional radiotherapy routinely adopts the shackle joint field，the single anterior forearm and the supraclavicular lymphatic drainage area，and the prescription dose is 3 cm below the center point.The shackle joint field and the chest wall electronic line field are collinearly connected on the skin.After the dose of the supraclavicular region reached 50 Gy，the axillary dose was calculated according to the depth of the central plane of the axilla，and the insufficient dose was supplemented by the sputum.
On the basis of the chest wall and the supraclavicular field，when the inner breast lymphatic drainage area needs to be irradiated，the inner breast is routinely irradiated with 9～12 MeV electron beam，and the first to third intercostal spaces are included.The inner boundary is the midline of the body，the outside is 5 cm on the affected side of the midline，and the upper boundary is connected with the lowerboundary of the supraclavicular field.The lower boundary is the lower edge of the 4th front rib.The outside and lower boundaries of the inner breast field are connected with the electronic line of the chest wall.
Fig.8-06 Body surface markers（A）and clavicular field mapping of conventional clavicular and chest wall fields in conventional two-dimensional radiotherapy（B）
8.3 Precise Radiotherapy for Breast Cancer
8.3.1 After Breast-conserving Surgery
At present，total breast irradiation has rarely been done in two-dimensional plans，and CT positioning is generally used to develop a three-dimensional radiotherapy plan（Fig.8-0-7）.When the CT simulator is positioned，the patient lies on the breast frame，the upper limbs are abducted，and the phantom is not fixed，and the marking line is directly drawn on the patient's skin.On the one hand，the fixation of the phantom increases the dose of the breast skin，and on the other hand，it easily causes the displacement of the breast，which in turn affects the accuracy of the treatment placement.In order to reduce the secondary error caused by the illumination field center position，the center of the whole breast irradiation is found at the time of positioning，generally placed in the nipple layer，and the marking line is drawn on the patient's skin（the marking line in the direction of the head and foot is as long as possible，beyond Breast range）.Because it is difficult to accurately distinguish the breast tissue range on the CT image，it is recommended to mark the anatomical boundary of the breast with the lead wire before the CT scan，and mark the surgical scar at the breast tumor bed with the lead wire，and then scans with 5mm layer.
Fig.8-07 Position and body surface markers of the patient during total breast radiotherapy.Positioning of the mammary gland outline and tumor bed scar before the CT scan
Target area of total breast radiotherapy：CTV：affected side of the breast，pectoralis major fascia.Excludes skin（received subcutaneous 0.5 cm），chest size muscles，ribs，and intercostal muscles（unless these sites are infested）.PTV：CTV is placed 0.5～1.0cm，and the skin direction is not released（limited to 0.5cm under the skin）（Fig.8-08）.Normal organs need to delineate the lungs，the healthy breast，the left anterior descending coronary artery and the left anterior descending coronary artery（left breast cancer patient）.The left anterior descending coronary artery（LAD）is emitted from the left main trunk of the coronary artery and travels in the interventricular sulcus.When CT scans，some can show，and some can not be displayed.When it cannot be displayed，it is drawn according to the position of the inter-chamber groove（Fig.8-09）.
Fig.8-08 Whole breast target area，blue：CTV，green：PTV
Fig.8-09 Left anterior descending coronary artery（red）
After the target area is drawn，the prescription dose and normal tissue limit requirements are submitted，and the physicist develops a radiotherapy plan.In order to protect the heart and lungs，the tangential field-based three-dimensional conformal plan（3DCRT）or the wild-field wild-strong plan（IMRT）is most commonly used.The 3D-CRT technique uses two tangential field illuminations with wedge plates.Different from the two-dimensional technique，the 3D-CRT has a three-dimensional dose distribution of the whole breast，a wedge plate according to the actual tissue density（lung correction），and conformal protection of the lung.Multi-sub-field IMRT technology is the wild-field radiation technique，also known as simplified intensity-modulated radiotherapy：on the basis of the conformal tangent field，6 to 8 subfields are added in the direction of the incision and the excision field to regulate the reduction of the high dose area inside.breast target area.80%of the total dose is still given by the two most basic conformal tangent fields.As with the two-dimensional radiotherapy technique，the two basic tangent fields are open 1 to 2 cm outward in the direction of the breast skin to ensure that during the irradiation.The entire breast is always in the field.The remaining 20%of the dose was administered by the subfield to reduce the volume of the high dose area and to evenly distribute the dose within the target area（Figure 8-10）.
Fig.8-10 Dose distribution map and DNH of total breast radiotherapy
8.3.2 Partial Mammary Gland Irradiation Technique
The pathological analysis of breast conserving patients after segmental resection showed that only 9%of the patients had tumor residue outside the residual cavity of segmental resection.Therefore，PBI needs to irradiate the tumor bed and the area of 1-2cm outside the tumor bed.PBI can be realized by the following methods：multi-tube tissue implantation brachytherapy，single-tube balloon brachytherapy（Mammosite），three-dimensional conformal external radiotherapy and intraoperative radiotherapy.
（1）Interorganizational implantation(https://www.daowen.com)
Intertissue implantation is a kind of multi-tube brachytherapy.One to several rows of catheterization can be performed during or after operation in the tumor bed and the area of 1-2cm.Then brachytherapy was performed according to the treatment plan.Radiotherapy can be irradiated with low dose rate（LDR）or high dose rate（HDR）.The prescription dose of low dose rate irradiation was 45-50Gy，4-5 day，and that of high dose rate irradiation was 32Gy/（8 times.4 days）or 34Gy/（10 times.5 days），twice a day.There are long follow-up results of PBI with intertissue implantation and brachytherapy：appropriate selection of patients，The radiotherapy side effects were small and the local recurrence rate was 1%～4.4%.However，the operation and treatment plan of interorganizational implantation is complex，which requires formal training and a long learning process，so it is difficult to be widely used.
（2）MammoSite
Mammosite is a single tube balloon brachytherapy device approved by the Food and Drug Administration，also known as intracavitary radiotherapy.Before the incision was closed or under the guidance of B-ultrasound，the balloon was placed in the residual cavity of breast tumor through a small scar incision or lateral incision.The advantage of balloon implantation after operation is that it has definite pathological diagnosis and reduces the rate of balloon relocation caused by unsuitable Mammosite for pathological reasons.When making the treatment plan，normal saline is injected into the balloon to make the shape of the balloon suitable for the residual cavity of the operation.The prescription dose was given to 1cm outside the surface of the balloon，most of which were 34Gy/（10 times for 5 days），high dose rate irradiation.At the time of treatment，radioactive sources can be used to stay at a single point or multiple points.The results of 1403 breast cancer patients treated with Mammosite reported by the American Surgical Association showed that 9%of the patients had good breast cosmetic effect 12 months after radiotherapy［14］.The early cosmetic effect was related to the minimum distance between balloon surface and breast skin.The cosmetic effect of patients with distance≥7mm was better than that of patients with＜7mm.8.1%of the patients had breast infection.With the accumulation of experience.The incidence of infection is getting lower and lower.3.4%of the patients report 3 weeks after radiotherapy existing radioactive memories of the skin.The 5-year follow-up results showed that the recurrence rate of intrabreast tumor was 2.9%.
8.3.3 After Radical Surgery
There are large individual differences in the anatomy of breast cancer patients.For example，the patient is fat and thin.The prescription depth of the supraclavicular area is 3 cm，which is not suitable for all patients.For patients with particularly thin chest wall，the electron line penetrates through the lung tissue deepr.Intensity-modulated radiotherapy technology can make the radiotherapy plan indivi dualized.Figure 8-11 shows the use of the tangential field-based intensity-modulation technology.Develop an overall intensity plan，or try VMAT or TOMO technology.The planning of this situation is very difficult.While ensuring the coverage of the target area and the uniformity of the dose，attention should be paid to reducing the dose of the heart and lung，while paying attention to ensuring the repeatability of the position.
Fig.8-11 Three-dimensional dose distribution of supracondylar region and chest wall radiotherapy after modified radical mastectomy for breast cancer
8.3.4 Radiotherapy for Respiratory Adaptation to Protect the Heart.
Although modern radiotherapy is used，there is no consistent conclusion whether postoperative radiotherapy for breast cancer will increase the risk of cardiovascular death in breast cancer.Marks found that the incidence of myocardial perfusion defect was 42%2 years after radiotherapy，which was related to the volume of cardiac irradiation［15］.Therefore，the volume of cardiac irradiation should be reduced as much as possible in order to reduce cardiac toxicity.IMRT can reduce the exposure volume of the heart.But for some patients whose hearts are close to the chest wall（heart anatomy is challenging），even IMRT can't avoid part of the heart（especially the left anterior descending branch of the ventricle and coronary artery）being exposed to a high dose of radiation.Breath-holding（DIBH）can inflate the lung after deep breath inhalation，and the heart moves backward and below，leaving the chest wall（Fig.8-11）.In recent years，physical dosimetry studies have shown that for patients with left breast cancer，breath-holding（DIBH）can reduce the volume of the heart in the irradiated field compared with free breathing，and DIBH can significantly increase the likelihood of death from radiation-induced heart disease（0.1%and 4.8%）［16］.Compared with free breathing，both free breath gated radiotherapy（end inspiratory gated）and DIBH can reduce the volume of cardiac irradiation.DBH technique is superior to end inspiratory gated therapy in protecting the heart..
Remouchamps reported the clinical experience of using ABC device to moderate inspiratory end breath holding（mDIBH）and conventional wedged plate tangent field in the treatment of 5 patients with left breast cancer.All patients could tolerate the treatment very well.Each treatment required 4 times and 6 times to hold breath，the median breath holding time was 22 seconds，and the median treatmenttime was 18 minutes.The positioning error in all directions is in 2.1～3.2mm［17］.DIBH is a promising radiotherapy technique for respiratory adaptation to protect the heart in patients with left breast cancer who are challenging cardiac anatomy.
Fig.8-11 Changes in cardiac position of CT scan in free breathing state and DIBH（blue is the left whole breast CT，red shown on CT in free breathing state is the whole heart in DBH state）
8.3.5 Case Report
Case 1.Female，53 years old
She was admitted to hospital in October 2018.Modified radical mastectomy was performed on 2018/11/01.Ⅰ-Ⅱ grade（mass size 2cm×1cm），intraductal carcinoma with focal intraductal carcinoma（about 20%of intraductal carcinoma）and axillary lymph nodes（10/21）were detected after operation.Immunohistochemical：ER（was about 70%+），PR（about 80%+），Cerb-B2（2+），FISH showed that HER-2 gene was not amplified，Ki-67（about 10%+）.
Postoperative diagnosis：pT2N3M0 ⅢC stage of invasive ductal carcinoma in the upper quadrant of left breast.
EC sequential T regimen chemotherapy was performed for 8 cycles after operation.
2019-07-10 operated postoperative radiotherapy，irradiation range and dose：left chest wall left upper and lower clavicle lymph node area，left internal mammary lymph node area，DT 50 Gy/25F，2 Gy/F.
Case 2.Female，35 years old
Diagnosis：pT2N1M0 ⅡB stage Luminal A after chemotherapy in left extramammary inferior quadrant invasive ductal carcinoma
Pathological diagnosis：2018-10-29“left breast mass puncture biopsy”.Pathological report：left breast puncture tissue（X201813553）：intraductal carcinoma with invasive carcinoma.Immunohistochemistry：the expression of invasive ductal carcinoma：ER（about 60%+），PR（about 60%+）and Cer-B2（+），Ki-67（about 10%）.“radical surgery for left breast cancer（sentinel lymph node biopsy for left breast cancer）was performed on 2018/10/31，and pathological report（B201810609）was diagnosed after operation（B201810609）.”radical surgery for left breast cancer（Sentinel lymph node biopsy for left breast cancer）was performed，and the pathological report（B201810609）was diagnosed as follows：（cut edge of left breast mass）Invasive carcinoma（size：2.5×1.0 cm），Immuno-histoche-mistry group：ER（medium+，80%），PR（medium+，80%），HER2（1+），ki-67（10%），supporting Ⅱ grade of invasive ductal carcinoma，no cancer was found on each incisor.Sentinel lymph nodes（1/5）showed cancer metastasis.
Case 3.Female，46 years old
Diagnosis：Luminal A in cT1N1MO IA stage after low grade intraductal carcinoma of left breast.
Auxiliary examination：2018/10/23 pathological diagnosis：left breast fiber cysticercosis with local ductal epithelial atypical hyperplasia.Combined with the results of immunohistochemistry，（left breast）fibrocystic breast disease，with common ductal hyperplasia and hyperhidrosis，cyst formation and inflammatory cell infiltration，flat epithelial atypical hyperplasia in small foci，atypical ductal hyperplasia and low grade intraductal carcinoma.The expression of intraductal carcinoma：ER（3+about 90%），PR（3+，about 90%），Cerb-B2（1+），ki-67（+，＜1%）.
8.4 Complications
8.4.1 Acute Radiotherapy Response
（1）Radioactive dermatitis
At 3～4 weeks of radiotherapy，the skin may have radioactive dry skin reactions such as pigmentation，hair follicle dilation，hair loss，erythema，edema，etc.；blistering，ulceration，etc.may occur on the 5th week after radiotherapy or 1～2 weeks after radiotherapy.The skin folds will be heavier，such as the chest wall near the armpit，the underlying breast folds，and the skin folds on the collarbone.When positioning，try to make the skin fold flat.The close-fitting clothes are soft and breathable during treatment，keeping the skin of the exposed field dry and clean.Do not use tape，alcohol，plaster，etc.in the skin of the field.When a wet skin reaction occurs，the local anti-inflammatory and swelling drug can be applied wet to avoid infection，and it usually heals in 2-3 weeks.
（2）Breast edema pain
After breast-conserving surgery，patients with whole breast radiotherapy may have breast edema pain in the late stage of radiotherapy and after the end of radiotherapy，especially in large breasts.When the patient takes a bath to wash the skin of the breast，it can aggravate the edema.Therefore，the patient should avoid squatting.Lighter need not be treated，severe cases can be treated with pain relief，or shortterm hormone swelling treatment.
（3）radiation pneumonitis
Most of them appear within 1 to 6 months after the end of radiotherapy，and very few appear in radiotherapy.The chest radiograph or chest ct shows a patch of lung exudation consistent with the radiotherapy field.Most patients are asymptomatic or have a dry cough，shortness of breath or fever.The incidence of symptomatic radiation pneumonitis is low，about 0～10%，mostly grade 2，and grades 4～5 are rare.
（4）Systemic response
Postoperative radiotherapy in breast cancer patients has little effect on blood.Patients after chemotherapy may have mild leukopenia during radiotherapy，and more dietary conditioning or Chinese medicine blood treatment.Fatigue is more common during radiotherapy，and it can be used to support the treatment.
8.4.2 Advanced Radiotherapy Injury
（1）Lymph edema of the upper limb of the affected side
Lymphedema is associated with axillary surgery and radiation therapy.After simple axillary lymph node dissection，about 10%of patients will have ipsilateral upper extremity edema.In the simple axillary radiotherapy，6%of patients will have ipsilateral upper extremity edema.Surgery plus axillary radiotherapy will increase the incidence of upper extremity edema to 31%.Mainly for prevention，no specific drugs.
（2）brachial plexus injury
Most occur after high-dose clavicle or axillary lymphatic drainage area.The incidence of brachial plexus injury is related to the total dose and division.The conventional supraclavicular area is 50Gy，and the incidence of brachial plexus injury is less than 1%at 2Cy/once.Therefore，clinically，patients with brachial plexus injury after the prevention of radiation dose should first be excluded from other causes，such as tumor recurrence.
Brachial plexus TD5/5 is 60Gy，that is，when the irradiation dose is 60Gy，5%of patients will have brachial plexus injury within 5 years after radiotherapy.Mainly for prevention，no specific drugs.
（3）ischemic heart disease
Early studies have found that patients with left breast cancer will be exposed to some heart and coronary arteries during radiotherapy，which will cause heart damage after radiotherapy.After 10 to 15 years of radiotherapy，the left side is more ischemic than the right breast cancer patient.Increasing mortality has offset the survival benefits of radiation therapy.With the improvement of radiotherapy technology，the mortality rate of heart disease decreased with the age of treatment，indicating that the risk of heart disease death caused by radiotherapy is gradually decreasing with modem radiotherapy technology.
（4）Breast cosmetic effect
Breast-conserving surgery patients should regularly evaluate breast cosmetic effects after radiotherapy.Breast cosmetic effects are related to patients，surgery，radiotherapy，and chemotherapy.
（5）Other
Subcutaneous tissue fibrosis，telangiectasia，radiation pulmonary fibrosis，rib fracture，second primary tumor such as lung cancer，contralateral breast cancer，sarcoma，etc.
（Li Wang）
8.5 References
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