The diagnosis of breast cancer should be considered to be ruled out in patients who visit the breast clinic, regardless of the presence or absence of clinical symptoms and abnormal signs. The outpatient physician needs to take a careful history, perform a breast examination, clarify the patient’s knowledge of his or her own breast, perform a breast cancer risk assessment, and conduct further tests according to the patient’s specific situation. With the gradual expansion of breast screening and mammography, more and more breast cancer patients are being diagnosed in the preclinical stage, which means that more and more histological biopsies will be needed to diagnose breast cancer. The clinical need to analyze the growth and dissemination of breast cancer in a comprehensive and detailed manner from the symptoms, signs and imaging manifestations of breast cancer, according to the biology of breast cancer and the characteristics of breast anatomy.
1. Symptoms.
The three most common symptoms of breast disease patients are breast lumps, abnormal lesions shown by ultrasound or mammography and breast pain. Breast pain is one of the main causes of breast disease in patients with breast disease. For premenopausal patients, ask about changes in breast pain before and after menstruation. Most breast pain is associated with hormonal irritation and swelling of the breast. The pain can radiate to the shoulders, upper extremities, and a burning sensation if muscle tension is present. More than 50% of women of childbearing age present with cyclic breast pain. For patients with breast pain, explanation and recommendation of physical therapy can be effective. Symptoms can be treated symptomatically in severe cases. Some breast pain manifests as pressure pain, which may be present in both benign fibrocystic lesions and malignant tumors, which are often combined with a more definite breast mass.
The first symptom of most primary breast cancers presents as a palpable breast lump, often first detected by the patient themselves. Most breast cancers present as a single, solid mass without pressure. Fibrous cystic masses, sometimes characterized by large and small, sometimes well-defined and sometimes indistinct masses. For breast masses in young women who cannot be characterized, observation of 1-2 menstrual cycles can also help in differential diagnosis.
Breast cancer can also present with symptoms such as skin thickening, depigmentation changes, axillary masses, and nipple discharge. Nipple discharge can be plasma, watery, milk-like, yellow, green, or bloody. Bloody discharge is often indicative of intraductal papilloma and occasionally bloody discharge in combination with papillary adenocarcinoma.
Nipple discharge is often suggestive of benign in the following cases.
1. Clear, or plasma, overflow involving 2 or more large milk ducts; non-self-induced overflow, requiring squeezing of the nipple to trigger overflow, and non-bloody overflow. Under normal circumstances, the milk ducts will also secrete a small amount of fluid. If the milk ducts above the collecting ducts are duced due to fibrosis or fluid thickening blocks, clinical signs such as milk duct dilatation and cyst formation may occur.
2. Diffuse skin erythema is mostly found in lactating mammary glands, and lactating patients with such symptoms are best treated with systemic antimicrobial therapy + local physical therapy. For non-lactating mammary glands with diffuse skin erythema, abnormally high white blood cell count and fever, breast abscesses are more likely and can be treated with systemic antimicrobial therapy, incision and drainage, or a combination of both. If there are no signs of infection in patients with diffuse skin erythema, a mammogram or biopsy is needed to rule out inflammatory breast cancer.
Due to the widespread availability of breast screening, an increasing number of patients with no clinical symptoms and abnormal imaging are being seen on an outpatient basis. It is recommended to classify imaging examinations and follow up with further examinations or follow-up according to different classification categories.
2. Physical signs.
Clinicians should inform patients how to perform breast self-examination and what problems should be seen in the hospital when breast self-examination occurs. However, a large randomized clinical trial including 266,064 women showed that between the 10th and 11th year of follow-up, 135 breast cancer patients died in the breast self-examination group and 131 in the control group, and breast self-examination did not reduce breast cancer mortality; breast self-examination substantially increased the detection rate of benign breast lesions. Breast self-examination is not a substitute for routine breast cancer screening, and this needs to be made clear to patients during outpatient visits.
The purpose of breast screening is to detect and evaluate breast abnormalities. Breast examination is performed by visualization and palpation. Positive signs include palpable breast masses (or lumps), glandular thickening (or nodular sensation), nipple discharge (without breast masses), and skin abnormalities.
Visual examination is performed to observe the appearance of the breast, the presence of skin and nipple abnormalities, and also to perform bilateral comparisons. Both localized elevation and localized depression (dimple sign) are suggestive of abnormalities, especially the latter, which often indicates superficial malignancy. Skin abnormalities include an orange peel appearance, erythema, and rupture. Diffuse breast erythema is usually considered inflammatory breast disease, but inflammatory breast cancer also often presents with skin erythema. Breast edema, orange peel-like appearance, and rupture are specific manifestations of locally advanced progressive breast. Careful observation of the nipple is needed. Nipple retraction, desquamation, and eczema-like changes should be excluded from nipple Paget disease.
During breast palpation, a thorough examination of the bilateral submammary rhomboids is performed in sequence. The patient is usually placed in the as or standing position, but may also be placed in the lying position. Do not grasp and pinch the breast, and when examining a pendulous breast, the breast may be held up for examination.
The most common abnormal sign associated with breast cancer on breast palpation is a breast mass. The location of the breast mass is recorded, usually according to the superior internal, superior external, inferior external, inferior internal, and central (areolar) areas. If the mass is located in the marginal area of the breast such as the axilla, lateral border of the pectoralis major muscle, subclavian, or parasternal, it needs to be described. Describe the number, shape, border, size, mobility, and texture of the masses. Breast gland thickening (nodular sensation) is different from breast masses, which can be large or small and have unclear borders. Good mobility of the mass often suggests a benign tumor, but there are exceptions. The relationship between the mass and the skin, pectoralis major fascia, and Cooper’s ligament needs to be carefully observed. Because of the presence of infiltration, breast cancers do not have an intact envelope and often move with the surrounding breast tissue when the mass is pushed. Larger breast cancers are often more fixed and are not difficult to identify clinically.
The presence of nipple overflow is examined during nipple palpation, and the number of overflow ducts (single duct, multiple ducts, unilateral nipple, bilateral nipple) and the nature of the overflow (colorless and clear, plasma, milk-like, brown, bloody) are recorded, and cytology is required for the overflow.
Lymph nodes in the axillary, subclavian and other breast drainage areas need to be carefully examined. Enlarged lymph nodes may indicate metastasis and can be a guide to the treatment plan and surgical options for breast cancer.
When patients present with symptoms related to breast cancer, or when breast masses are found on their own breast examination or clinical breast examination, they need to be differentiated and diagnosed differently from benign and malignant tumors from medical history, physical examination, imaging examination and histological examination.
An informative medical history can provide clues. The time of finding breast mass, the speed of growth, the change of tumor during menstrual cycle, the presence of inflammatory manifestations on the skin of the surface of the mass, whether regional lymph node enlargement is found, nipple scratching and eczema-like changes, and the color and shape of nipple overflow may all suggest the diagnosis of malignant tumor. Pay attention to asking the patient’s past history, family history, and menstrual fertility for the presence of risk factors for breast cancer, such as history of chest radiation therapy, family history of breast cancer, presence of individual genetic predisposition (brca gene), risk factors confirmed by Gail’s breast cancer risk assessment model (age, age at menarche, age at first childbirth or absence of childbirth, number of previous biopsies for benign breast tumors, previous breast biopsy-confirmed atypical hyperplasia and/or lobular carcinoma in situ, race), etc.
With the gradual development of breast cancer screening in the country and the increase of women’s awareness of breast self-examination, tumors may be diagnosed when the diameter is small. At this time, the differential diagnosis of benign and malignant tumors mainly refers to the results of imaging and histological examination.
1.Mammary swelling.
For patients with clinically detected breast masses or breast lumps, the diagnosis is made in different order of examination according to the patient’s age. the age groups recommended by NCCN are under 30 years old group, 30 years old and over 30 years old group.
(1) 30 years and older group.
Patients aged 30 years and older with breast masses have a significantly increased risk of breast cancer. Clinical observation alone is not sufficient and bilateral mammography is recommended to be performed first. The lesions were treated separately according to the BI-RADS classification of the lesions.
For BI-RADS category 1, 2 and 3 lesions, breast ultrasound is performed. For lesions in categories 4 and 5, the correlation between clinical examination and imaging was carefully analyzed. If there is no correlation between the mass found on clinical examination and the lesion shown on mammography, continue the examination according to BI-RADS category 1, 2, and 3 lesions. If the clinical examination is consistent with the mammographic findings, a histological diagnosis is obtained by coarse needle aspiration or fine needle localization of the mass for excision.
For BI-RADS category 1, 2, and 3 lesions, if the ultrasound examination is suspicious for malignancy, or if the benignity or malignancy cannot be determined, coarse needle aspiration or fine needle localization of the mass is recommended to obtain a histological diagnosis. If the histological examination is determined to be benign and the ultrasound findings are compatible, a clinical examination every 6-12 months and a follow-up of 1-2 years are recommended (follow-up plan 1), which can be combined with ultrasound examination. If the mass gradually increases in size during the follow-up period, surgery is recommended; if the mass does not change significantly, routine screening for breast cancer should be performed. If the histological examination is difficult to determine the benignity or malignancy, atypical hyperplasia, benign lesion but microscopic heterogeneity, or LCIS, close follow-up is needed after surgical excision. For patients with atypical hyperplasia and LCIS, medications are recommended to reduce the risk of breast cancer. When malignancy is determined on histological examination, the treatment protocol for breast cancer is followed.
When a single benign lesion is detected by ultrasound, surgical excision, coarse needle aspiration or clinical observation can be performed. It is recommended that only patients with benign lesions less than 2 cm in diameter be followed up according to follow-up protocol 1, which can be combined with ultrasound or mammography to assess the stability of the tumor. Those with benign lesions determined by surgical excision are followed up according to the conventional breast cancer screening protocol. For patients with atypical hyperplasia and LCIS, medications are recommended to reduce the risk of breast cancer. When histological examination is determined to be malignant, follow the treatment protocol for breast cancer. If the histological examination by coarse needle aspiration is benign, follow the follow-up protocol1, which can be combined with ultrasound or mammography to assess the stability of the tumor. During the follow-up period, the mass gradually increases in size and histological examination is performed again. If the lesion is difficult to characterize, atypical hyperplasia, or benign lesions combined with cellular anomalies, excision of the mass is recommended.
Simple cysts suggestive of asymptomatic cysts on ultrasonography can be observed for 2-4 months, and the patient’s symptomatology is the need for clinical management. If the ultrasound suggests a complex cyst, puncture is recommended, followed by a short clinical follow-up (follow-up protocol 1) + mammography (± mammography). Histological examination is required if the mass gradually increases in size during follow-up. If the swelling disappears after puncture and bleeding fluid, 2-4 months of clinical follow-up is required; if the swelling cannot be palpated by breast examination, follow the routine breast cancer screening protocol. If bleeding fluid is pierced, the cyst does not disappear after puncture, or if ultrasound suggests a cystic solid mass (complexcyst), imaging-guided tissue biopsy or surgical excision is recommended. If the histological examination suggests a benign lesion with no obvious cellular anisotropy, follow-up is performed according to the follow-up protocol1, which can be combined with ultrasonography. If the mass gradually increases in size during the follow-up period, a second histologic examination is required; if the mass is stable, breast cancer screening is performed according to the usual protocol. If the histological examination suggests a benign lesion but there is cellular anisotropy, difficult to characterize, atypical hyperplasia, or LCIS, excisional biopsy is recommended. If the histological examination after excisional biopsy suggests benign, breast cancer screening will be performed according to the conventional protocol; if the histological examination suggests atypical hyperplasia or LCIS, the risk of breast cancer will be reduced by taking medication in addition to the conventional screening; malignant tumors will be treated according to the standard of breast cancer treatment.
If no breast abnormality is detected by ultrasound, histological examination can be performed, and clinical follow-up can also be performed: once every 3-6 months, and 1-2 years continuously (histological examination is recommended if the mass gradually increases during the follow-up period of the follow-up program; if the mass is stable, follow up according to the conventional breast cancer screening method.
(2) Under 30 years old group.
Breast ultrasound is preferred for patients with breast masses under 30 years of age. The differential diagnosis after ultrasound was performed according to the method for the 30 and over 30 years old group. In particular, mammography should be considered only in certain specific cases. patients under 30 years of age are less likely to be malignant, and it is better to follow up 1-2 menstrual cycles for breast masses that are clinically suggestive of benignity. if the mass disappears after 1-2 menstrual cycles, follow up in the usual way; if the mass persists, ultrasonography should be performed again. Puncture biopsy prior to ultrasonography is not recommended.
2. Nipple overflow without breast swelling.
Bilateral nipple overflow with milk-like fluid needs to be excluded for pregnancy and endocrine disorders. Some medications can also induce bilateral nipple overflow, these include: psychotropic drugs, antihypertensives, opioids, oral contraceptives, estrogen, etc. For female patients under 40 years of age with bilateral nipple multiductal overflow, clinical follow-up is sufficient, along with advice not to squeeze the breast and to consult immediately if the nature of the overflow changes. for patients over 40 years of age, mammography should be performed first and then according to BI-RADS classification for Treatment.
Persistent spontaneous unilateral nipple-monoductal overflow requires clinical attention. Regardless of the shape of the overflow (clear, plasma, bloody, etc.), guaiactest and cytology are required. Mammography is recommended for all patients and is managed according to the BI-RADS classification. Ultrasonography is also possible. For BI-RADS 1, 2 and 3 lesions, mammography is performed and the procedure is selected based on the findings. For BI-RADS category 4 and 5 lesions, the standard treatment procedures for breast cancer are performed. If the diagnosis is benign, or if it is not possible to determine benign or malignant, a mammogram is performed and the resection method is chosen based on the findings of the mammogram. If the diagnosis is malignant, the treatment protocol for breast cancer will be followed. If the result of mammography is negative, diagnostic surgery should be considered.
3. Asymmetric thickening.
Localized thickening of the breast, nodular sensation, asymmetry and breast masses are different, and it is difficult to define the extent of the lesion during mammography. If the patient is under 30 years old and has no risk factors for breast cancer, ultrasound examination is performed first. If there is a clinical need to exclude malignancy, mammography may also be performed. Diagnostic mammography is rarely needed at this time due to the difficulty of visualizing breast density and the low risk of breast cancer.
In patients 30 years of age and older, mammography is performed first and may also be combined with breast ultrasound. Thickening, nodularity and asymmetry of the breast are evaluated based on the results of mammography.
If no abnormalities are seen on mammography and ultrasound, clinical evaluation will be repeated at 3-6 months. Annual screening is recommended if there is little change in the lesion. Histological examination is recommended if the lesion appears to be progressive, or if malignancy is a possibility, or if mammography suggests BI-RADS category 4-5 lesions.
4. Skin changes.
Abnormal changes in the skin of the breast are a risk sign and require clinical evaluation. Mammography is performed first and can be combined with ultrasonography. Depending on the results of the mammogram, the next step in management is decided. Even if there are no abnormal findings on mammography, further investigations are still needed.
Puncture biopsy or nipple biopsy is required for BI-RADS category 1, 2, and 3 lesions with no significant abnormalities on ultrasound or only suggestive of simple cysts. The decision to use antibiotics is based on the clinical presentation, but further diagnosis of the lesion cannot be stopped during the use of antibiotics. If a biopsy suggests a benign lesion, histological examination is performed after a second history and mammogram and, if necessary, a consultation with a breast specialist and an MRI of the breast, and histological examination is required for BI-RADS 4 or 5 lesions, or if ultrasound suggests a lesion other than a simple cyst. In this case, histological examination is obtained by coarse needle aspiration or surgical excisional biopsy. Cysts with thickened cyst walls and cystic solid lesions require excisional biopsy. If the skin histological examination suggests malignancy, treatment will be according to the standard of breast cancer treatment.
5.Summary.
Clinical judgment of breast lesions is an important part of choosing the best treatment plan. If the physical examination of the breast, imaging and pathology findings are inconsistent with each other, the clinician needs to reassess the patient’s possible problems and benefit the patient through further management.