Special types of breast cancer, also known as special forms of breast cancer, have different clinical characteristics from common breast cancers and have special features in diagnosis, treatment and prognosis. This article briefly introduces the diagnosis and treatment of three special types of breast cancer: inflammatory breast cancer, breast Paget’s disease, and lobulated breast tumor.
Inflammatory breast cancer (IBC)
IBC is a clinical syndrome of invasive breast cancer, which is highly invasive, malignant, prone to distant metastasis and has a poor prognosis, and has been considered as a lethal disease. However, there is now ample evidence that IBC is a different disease from locally advanced breast cancer of non-inflammatory breast cancer. IBC accounts for approximately 1-6% of all breast cancers in the United States. Because of the low incidence of the disease, the difficulty of obtaining enough cases for clinical studies in a single center, and the lack of high-level evidence-based medicine, IBC has not progressed as rapidly as other breast tumors, and the current understanding of this disease is still mostly obtained from retrospective studies and prospective studies of small samples.
The pathogenesis of IBC is the blockage of lymphatic vessels in the skin by cancer cells, which leads to increased pressure and stagnation in the vasculature, resulting in erythema, edema and skin thickening in the breast. The first symptoms are usually enlarged, red, firm and orange peel-like appearance of the breast, and the skin is sometimes visible with obvious dandruff-like edges or mottled pigmentation. MRI is mainly used in cases where the breast lumps are not detected by ultrasound. IBC is prone to distant metastases such as lung, liver and bone, so CT examination of the chest and upper abdomen and bone scan should be performed routinely, and the recent PET/CT examination is useful for detecting distant metastases.
The clinical diagnosis of IBC is made based on the rapid development of the disease, congestion and edema of more than 1/3 of the skin of the breast (orange peel sign), and obvious palpable borders in the congested area, often without obvious palpable masses, etc. However, fine needle aspiration or pathological examination is required to find cancer cells in the red and swollen area to confirm the diagnosis. Skin biopsy can reveal extensive cancer cell invasion in the skin and subcutaneous lymphatic vessels. It should be noted that the diagnosis of IBC can be based on its clinical manifestations, although biopsy is required to assess the presence of tumor in the breast and dermal lymphovascular invasion (DLI), DLT is not necessary for diagnosis and is not sufficient to diagnose the disease, rather a negative DLI specimen cannot exclude the diagnosis of IBC, because the distribution of tumor cells in the vasculature is irregular and false negatives may occur. In fact, the clinical detection rate of DLI is less than 75%. There is no specificity in the pathological histological type of IBC, and various histological subtypes can be seen in IBC, but the most common one is high-grade ductal carcinoma. Since preoperative chemotherapy should be performed after the diagnosis of IBC, biopsies should be examined for hormone receptor status, Her-2 status, DNA content and S-stage fraction in addition to routine pathological examination.
ICB should be differentiated firstly from acute mastitis and breast abscess, which can be confirmed by cytological or pathological examination of the lump puncture in addition to the typical history and signs; secondly, it should be differentiated from malignant lymphoma or leukemic breast infiltration, which are more difficult to distinguish clinically and require cytological or histological examination to confirm the diagnosis; most importantly, it should be differentiated from locally advanced non-inflammatory breast cancer with co-infection, because IBC has a poorer prognosis than the latter, even though In addition, the average age of onset of IBC is younger, with a peak incidence at age 50 years, while the incidence of co-infected locally advanced non-inflammatory breast cancer continues to rise after age 50 years. The incidence of locally advanced non-inflammatory breast cancer with co-infection continues to rise after age 50.
According to the AJCC Cancer Staging (6th edition) the primary lesion of IBC is designated as T4d, and the stage of IBC is designated as IIIB, IIIC or IV depending on lymph node involvement and the presence of distant metastases.
IBC is highly aggressive, with 30% of distant metastases at diagnosis, a local recurrence rate higher than 50% with surgery alone or combined radiotherapy, a median survival of 6-15m, and a 5-year survival rate lower than 5%. In the last 30 years, the median survival has increased to 40m and the 15-year survival rate has increased to 20-30% by using the integrated treatment model of preoperative chemotherapy, surgery and postoperative radiotherapy. The best preoperative chemotherapy regimen has not yet been established, but regimens containing anthracyclines and paclitaxel have shown better efficacy, and studies have shown that chemotherapy efficacy is significantly correlated with survival and local control rate, and pCR is an important prognostic indicator. preoperative chemotherapy for IBC with good efficacy, followed by surgery and local radiotherapy can significantly improve 5-year survival rate, local control rate and survival without distant metastasis.
The International Panel of Inflammatory Breast Cancer Consensus on Inflammatory Breast Cancer Diagnostic and Treatment Criteria recommends: an anthracycline- and paclitaxel-containing regimen is the standard preoperative chemotherapy regimen for IBC, and Her-2 positive patients should be treated with trastuzumab in combination with at least 6 cycles of preoperative chemotherapy for 4-6 months, and the efficacy should be evaluated by physical examination and imaging examination in a timely manner. The standard procedure is modified radical surgery, breast-conserving surgery is limited to clinical studies, and the timing of breast reconstruction is still controversial, immediate breast reconstruction is not recommended at present; all IBC patients should undergo radiotherapy after surgery, and the radiotherapy area should include: supraclavicular area, internal breast lymph node area, and for recurrent patients who are younger than 45 years old, have positive or too close cut margins, still have ≥4 positive lymph nodes after preoperative chemotherapy, and are insensitive to preoperative chemotherapy The recommended TD for high-risk patients should be up to 66 Gy, and the skin dose should be adjusted to alleviate the acute skin reaction caused by radiotherapy. Trastuzumab treatment should be continued during radiotherapy for Her-2-positive patients; systemic treatment after radiotherapy includes: chemotherapy, endocrine therapy selection for hormone receptor-positive patients with reference to general breast cancer, and trastuzumab treatment for Her-2-positive patients for a total of 1 year.
Paget’s disease of the breast
Paget’s disease of the breast was first described by Paget in 1874: tumor cells were found in the epidermis of the nipple-areola complex (NAC) before the discovery of breast cancer. Paget’s disease of the breast is a specific type of breast cancer that accounts for about 1 to 3 percent of primary breast cancers. The rarity of the disease and its easy confusion with other skin diseases often leads to delayed diagnosis. Although most Paget’s disease of the breast is slow to develop, has a low malignancy and a good prognosis, 80%-90% of patients have associated tumors in other parts of the breast, which may not necessarily occur near the NAC and can be either in situ or invasive.
Paget’s disease of the breast often has no conscious symptoms or only pruritic discomfort, so it is generally not easy to attract the attention of patients. The typical manifestation is eczema-like changes in the NAC, which may start with abnormal sensation, itching or burning sensation, followed by pain, erythema, desquamation, erosion, oozing, bleeding and crusting in the nipple, which may be accompanied by nipple overflow and blood spillage, often recurring several times, with palpable lumps under the areola and even nipple invagination, and palpable enlargement of axillary lymph nodes. The disease is easily misdiagnosed as some benign skin diseases such as nipple eczema and dermatitis in the early stages, so any woman over 40 years of age with unprovoked nipple erosion that does not improve after several weeks of treatment should consider a surgical biopsy to clarify the diagnosis.
Patients with clinical manifestations of suspected breast Paget’s disease should undergo a full epidermal surgical biopsy of the skin of the NAC, which must include at least a portion of the clinically involved NAC, and a physical examination, mammography, ultrasound, MRI, and other adjuvant examinations, as well as a biopsy to determine whether there is a combined tumor in the breast.
There are three types of Paget’s disease in the breast: (1) simple Paget’s disease in the breast, (2) Paget’s disease in the breast combined with intraductal carcinoma, and (3) Paget’s disease in the breast combined with invasive carcinoma. Treatment strategies should be developed according to the different types.
Simple Paget’s disease of the breast belongs to carcinoma in situ and should be completely operated after diagnosis. The surgical margins must be free of diseased tissue by pathological examination to prevent postoperative recurrence. Postoperative breast radiotherapy is given to the NAC, and tamoxifen endocrine therapy is considered for hormone receptor positive patients to reduce the risk of recurrence, and those with positive lymph nodes are treated as invasive breast cancer.
Paget’s disease of the breast combined with intraductal carcinoma of the breast, both of which are in situ, can be treated by total mastectomy + axillary staging, or breast-conserving surgery with total NAC + intramamammary tumor, and ensuring negative breast tissue and tumor margins under the NAC, followed by breast radiotherapy, with push radiotherapy to the NAC and tumor site, and tamoxifen endocrine therapy for hormone receptor positive patients to reduce the risk of recurrence. Those with positive lymph nodes should be treated as invasive breast cancer.
For Paget’s disease of the breast combined with invasive breast cancer, the patient should be treated as invasive carcinoma, with total mastectomy + surgical staging, or breast-conserving surgery with total NAC + internal breast tumor + surgical axillary staging, and ensuring negative breast tissue and tumor margins under NAC. Breast Cancer.
Phyllodes tumors of the breast cancer (PTB)
PTB is a rare fibroepithelial tumor, accounting for 0.3%-0.9% of all breast tumors and only 2%-3% of fibroepithelial tumors. The onset of PTB is 20 years later than that of fibroadenoma, and the average age of onset reported abroad is 41-44 years.
The main clinical feature of PTB is a painless solitary mass, mostly located in the upper outer quadrant, usually unilateral, with equal incidence on the left and right. The mass usually does not invade the pectoral muscle and skin, has good mobility, has an insidious onset, progresses slowly, and has a long course, sometimes the mass grows rapidly within a short period of time resulting in dilated skin veins on the surface of the tumor, but papillary retraction is rare, and axillary lymph node metastasis is also rare.
In PTB, preoperative mammography, ultrasonography and fine needle aspiration histopathology can be performed. mammography in PTB shows a solid mass with clear borders or occasionally lobulated, with coarse calcified spots within the mass and a translucent halo around the mass, which is due to the compression of the interstitium around the tumor. On ultrasound examination of the breast, lobulated tumors have clear borders with homogeneous hypoechogenicity and may have cystic degenerative areas. Ultrasound and mammogram images of this disease are similar to those of fibroadenoma, but puncture cytology and intraoperative freezing are often unable to confirm the diagnosis due to the small amount of tissue, so the diagnosis of this disease is mainly based on postoperative pathology.
The WHO classifies PTB as benign, junctional and malignant based on the histological characteristics of lobulated tumors. (See table below)
Histologic classification of lobulated tumors (WHO , 2003)
Observed indicators Benign Junctional Malignant
Mesenchymal cell hyperplasia Few Few Significant
Mesenchymal cell pleomorphism Mild Moderate Obvious
Number of nuclear schizophrenia Few Moderate Many (>10)
Tumor margin Clearly defined Distended growth Infiltrative growth
Mesenchymal distribution Homogeneous mesenchymal distribution Uneven mesenchymal distribution Obvious mesenchymal hyperplasia
Heterogenous mesenchymal differentiation Rare Rare Common
Surgical resection is the preferred treatment for PTB, and the surgical approach can be decided according to the size of the mass and the breast, using either mass excision or partial mastectomy. The most common form of PTB recurrence is local recurrence. Distant metastasis usually occurs in the lung, and the positive rate of axillary lymph nodes is only 1%-2%. Therefore, unless clinical examination or pathological detection reveals lymph node lesions, lymph node dissection is generally not necessary, and those with distant metastasis are treated as soft tissue sarcoma.
Most lobulated tumors have an ER-positive (58%) and/or PR-positive (75%) epithelial component, but the role of endocrine therapy in lobulated breast cancer has not been proven, and similarly, there is no evidence that adjuvant chemotherapy can reduce recurrence or mortality rates. As for radiotherapy, its exact effect is unknown, but adjuvant radiotherapy has been proposed for patients who cannot be guaranteed ≥lcm negative margins or who have interstitial overgrowth and tumor diameter >5cm.
In conclusion, the characteristics of these three specific types of breast cancer are: inflammatory breast cancer: highly invasive, poor prognosis, the best treatment mode is: preoperative chemotherapy to shrink the tumor to the extent that it can be operated, followed by mastectomy and radiotherapy; paget’s disease of the breast: simple NAC lesions, slow development, good prognosis, but the presence or absence of combined intramamammary tumors and the type should be clarified and treated as invasive or in situ cancer, respectively; lobular tumors of the breast: good prognosis, adjuvant radiotherapy. Lobular tumor: good prognosis, local surgery is the main focus.