Breast cancer (mastocarcinoma) is the most common form of cancer among women. Consequently, it will be encountered by doctors as part of their work in hospitals and medical practice. This disease exhibits a heterogeneous pattern including different histological subtypes, which may differ considerably in their degree of malignity and, consequently, in their clinical symptoms and therapy. The following article helps you to understand the clinical picture of mastocarcinoma, identify its symptoms and to classify its histology correctly.
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Breast Cancer

Bild: “Breast Cancer” by BruceBlaus. License: (CC BY-SA 4.0)

Definition of Mammary Carcinoma

The mastocarcinoma is a malignant disease of the mammary gland.

The mastocarcinoma, also known as breast cancer, is a malignant tumor of the mammary gland. The point of origin may either be the mammary ducts or the gland’s lobules. Correspondingly, the ductal carcinoma is distinguished from the lobular carcinoma.

Epidemiology of Mammary Carcinoma

Diagram showing the lobes and ducts of a breast

Image: “Diagram showing the lobes and ducts of a breast” by Cancer Research UK. License: (CC BY-SA 4.0)

The mastocarcinoma in human population

The mastocarcinoma, accounting for 25% of all malignant diseases among women, is the most common form of cancer among women. The yearly incidence adds up to 110 cases per 100,000 women.

Note: One out of 8 to 10 women gets breast cancer during her lifetime!  The chances of becoming diseased with breast cancer increase with age, but young women also can be affected. It usually affects women between the ages of 60 – 80.
Note: In the western hemisphere, the most common cause of death among women in their 35th – 55th year of life is the mastocarcinoma!

However, not only women get breast cancer: 1% of mastocarcinomas affect men.

Age-standardised death rates from Breast cancer by country (per 100,000 inhabitants)

Image: “Age-standardised death rates from breast cancer by country (per 100,000 inhabitants)” by Lokal_Profil. License: (CC BY-SA 2.5)

Etiology of Mammary Carcinoma

Causes of the mastocarcinoma

The exact etiology is unknown, but it is assumed to be a multifactorial event. Among genetic factors, varying lifestyle habits appear to play a role. The majority of mastocarcinomas forms spontaneously (= sporadically, about 95%), whereas only a minor fraction is of hereditary origin, in terms of familial genetic modifications (about 5%).

Risk factors for the mastocarcinoma

There are multiple risk factors, which may promote the formation of breast cancer.

The most important population-related risk factor for the formation of breast cancer is advanced age.

With higher age, the risk of contracting a mastocarcinoma increases. However, also endogenous or exogenous hormonal influences as well as family history, diet and lifestyle play a decisive role. The following table gives you an overview:

Risk factors
Diet/lifestyle Large amounts of meat and fat, overweight/obesity (especially after menopause), high intake of alcohol and cigarettes
Family history Mastocarcinoma in first or second degree relatives (mother, grandmother, sister)
Hormonal influences Long hormone exposure: early menarche and late menopause; higher age at first delivery (> 30 years of age), nulliparity, hormone replacement therapy after menopause (> 5 years), oral contraceptives (disputable)
Others Mastocarcinoma on contralateral side, ionizing radiation, benign findings in a biopsy, mastopathy, hyperprolactinaemia

In the majority of hereditary mastocarcinomas, a mutation on one of the following two tumor suppressor genes can be found. The genes are the “Breast-Cancer-Gene” BRCA-1 (on chromosome 17q) and BRCA-2 (on chromosome 13q).

Representation of the BRCA1 gene on chromosome 17

Image: “Representation of the BRCA1 Gene on Chromosome 17.” by Kuebi. License: (CC BY-SA 3.0)

Note: Women having a mutation of the BRCA-1 or BRCA-2-gene run a higher risk (80 – 90%) to get affected by mastocarcinoma. In the case of such mutation, also risks for ovarian cancer are increased.

Classification of Mammary Carcinoma

WHO-classification of the mastocarcinoma

The mastocarcinoma is classified in the WHO-classification (1981) into ductal and lobular carcinomas by identifying the histological phenotype which may emerge preinvasive (in-situ) or invasive.

Note: The majority of carcinomas have a ductal genesis (85 – 90%)!  The following list gives an overview of the WHO-classification:
Non-invasive transformations Intraductal carcinoma (DCIS = ductal carcinoma in situ), lobular carcinoma in situ (LCIS)
Invasive transformations Invasive ductal mastocarcinoma, invasive lobular mastocarcinoma, invasive ductal mastocarcinoma with defined differentiation: mucinous, medullary, papillary, tubulary, adenoid-cystic, secretory, apocrine; metaplastic carcinomas
Special types Paget’s disease of the nipple, inflammatory carcinoma

TNM-classification of the mastocarcinoma

The TNM-classification is an important instrument to classify malignant tumors with regard to their spreading, affection of regional lymph nodes and the presence or absence of distant metastases. Using this classification, the further procedure regarding the method of treating is determined.

The following table depicts the TNM-classification of the mastocarcinoma using the classification of the UICC (Reference: Diagnostic Breast Center Munich).

T – Primary tumor TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
Tis(DCIS): Ductal Carcinoma in situ
Tis(LCIS): Lobular Carcinoma in situ
Tis(Paget): Paget’s disease of the nipple without a trackable tumor in the underlying breast parenchyma
T1: Tumor with less than two cm maximum dimension
T1mi < 0,1 cm (micro invasion)
T1a > 0,1 cm and  ≤ 0,5 cm
T1b > 0,5 cm and ≤ 1,0 cm
T1c > 1,0 cm and ≤ 2,0 cm
T2: Tumor > 2 cm but < 5 cm in greatest dimension
T3: Tumor > 5 cm in greatest dimension
T4: Tumor of any size with direct extension to the skin or chest wall (i.e. muscles between the ribs (intercostal muscles), ribs, but not the pectoral muscles)
T4a Extension to chest wall
T4b Edema or ulcerations of the skin, including skin metastases
T4c Both T4a and T4b
T4d Inflammatory mastocarcinoma (inflammatory breast cancer)
pN – Regional lymph nodes pNX: Lymph nodes cannot be assessed, because they were not removed or already removed previously
pN0: No regional lymph node metastasis
pN1mi: Micrometastase(s) (> 0,2 mm and ≤ 0,2 mm) in 1 – 3 ipsilateral axillary lymph nodes and/or ipsilateral lymph nodes alongside the internal mammary artery
pN1a: Metastase(s) (> 0,2 mm) in 1 – 3 ipsilateral axillary lymph nodes
pN1b: Metastase(s) (> 0,2 mm) in ipsilateral lymph nodes alongside the internal mammary artera without metastases in axillary lymph nodes
pN1c: Metastase(s) (> 0,2 mm) in 1 – 3 ipsilateral axillary lymph nodes and ipsilateral lymph node(s) alongside the ipsilateral internal mammary artery
pN2a: Metastases (> 0,2 mm) in 4 – 9 ipsilateral axillary lymph nodes
pN2b: Metastase(s) (> 0,2 mm) in 4 – 9 ipsilateral lymph nodes alongside the internal mammary arteria without metastases in axillary lymph nodes
pN3a: Metastases (> 0,2 mm) in 10 and more ipsilateral axillary lymph nodes or in ipsilateral infraclavicular lymph nodes
pN3b: Metastase(s) in clinically detected lymph nodes alongside the internal mammary artera in the presence of at least one axillary lymph node metastase or lymph node metastases in more than three axillary lymph nodes and in lymph nodes alongside the internal mammary artery
pN3c: Metastase(s) in ipsilateral supraclavicular lymph nodes
M – Distant metastases M0: No distant metastases
M1: Distant metastases, if applicable, including specification of the organ affected by metastasis.
Lung PUL, bones OSS, liver HEP, brain BRA, lymph nodes LYM, bone marrow MAR, pleura PLE, peritoneum PER, adrenal glands ADR, skin SKI, other organs OTH

Pathology and Pathophysiology of Mammary Carcinoma

Histological examination of mastocarcinoma

Invasive Lobular Carcinoma of the Breast

Image: “Invasive Lobular Carcinoma of the Breast” by Ed Uthman. License: (CC BY 2.0)

As already mentioned, the mastocarcinoma is classified in ductal or lobular and invasive or non-invasive (in-situ) types. The DCIS and the LCIS remain locally and do not break through the basal membrane, whereas invasive carcinomas infiltrate the surrounding tissues. After a period of latency, the in-situ-carcinomas may develop into an invasive carcinoma. The most frequent one is the adenocarcinoma. 

Diagram showing ductal carcinoma in situ

Bild: “Diagram Showing Ductal Carcinoma in situ (DCIS)” von Cancer Research UK. Lizenz: (CC BY-SA 4.0)

The DCIS originates from the mammary ducts of the mammary gland and may be differentiated differently: solid (most frequently), comedo-type, cribriform or papillary. The various subtypes are different in their developing, prognosis and therapy.

In the case of the DCIS central necrosis may develop into calcium-precipitation (“micro-calcification”), which can be critical for diagnostics. The period of latency of the invasive ductal carcinoma is about 10 years.

Diagram showing lobular carcinoma in situ

Image: “Diagram Showing Lobular Carcinoma in situ (LCIS)” by Cancer Research UK. License: (CC BY-SA 4.0)

The LCIS originates from monomorphic cell proliferation with small tumor cells in the lobules of the mammary gland. The acini extend to a bulb-shaped form. The period of latency before transformation into an invasive lobular carcinoma is, being up to 25 years, longer than the period of latency of the DCIS, for which reason the LCIS is also named a pre-cancer. Often it is multi-centric.

Clinical Symptoms of Mammary Carcinoma

Localization and metastasis of the mastocarcinoma

Breast quadrant – breast cancer

Image: “Breast Quadrant – Breast Cancer” by Cadelli. License: Public Domain

Accounting for about 55%, the mastocarcinoma is most frequently located in the upper outer quadrant of the breast, whereas it is located retro-areolar in 15%, in the upper inner in 15% and in the lower outer quadrant in 10% of the cases. The lower inner quadrant is affected very rarely, amounting to only 5%.  

A carcinoma is multifocal, multiple foci in the same quadrant are present, if it is multi-centric, different quadrants are affected. Furthermore, the contralateral breast may as well be affected by a tumor, which occurs in about 5 – 10% of the cases.

Mastocarcinomas can metastasize at an early stage:

Lymphogenous into regional lymph nodes of the axilla, hematogenous into the skeleton (most common), the lung, the liver or the brain. Also, metastasis into the ovaries is possible.

Diagram showing most common sites breast cancer spreads to

Image: “Diagram showing most common sites breast cancer spreads to” by Cancer Research UK. License: (CC BY-SA 4.0)

Affected axillary lymph nodes are used as an indicator of a hematogenous metastasis. During further procedures, examinations that verify metastases in organs should follow. For this, a chest X-ray, ultrasonic examination of the liver and bone scintigraphy is used.

Symptoms of the mastocarcinoma

A dense palpable lump in the breast, which is detected by the patient herself in the majority of cases, is the leading symptom of the mastocarcinoma. Further symptoms, partially not occurring before reaching more advanced stages, are the following:

Early signs of breast cancer

Image: “Early Signs of Breast Cancer” by Morning2k. License: Public Domain

  • Changes in size and shape, asymmetry of the breast
  • Eczema of the nipple (always needs clarification!)
  • Swelling of the tumor
  • Dimpled skin (plateau phenomenon)
  • Orange-peel-skin (peau d’orange)
  • Retraction of the nipple
  • Bloody secretion out of the nipple
  • Swollen axillary lymph nodes
  • Localized chest pain (rarely)
Note: A palpable node always needs to be tested.

Special Types of Breast Cancer

The special types of the mastocarcinoma, to which the inflammatory mastocarcinoma and the Paget’s disease of the nipple belong, will be outlined briefly in the following.

Inflammatory breast cancer

The rapidly progredient inflammatory mastocarcinoma is an aggressive type of breast cancer and is based on a lymphangiosis carcinomatosa. Clinically, it is characterized by an erythema of the skin, orange-peel-skin, and swelling and reddening of the breast’s skin.  

Inflammatory Breast Cancer

Image: “(a) inflammatory breast cancer (IBC) case (b) IBC; erythema, edema and peau d’orange of the right breast, no tumor mass, duration of signs is 1 month; (c) IBC; erythema, edem, peau d’orange of the left breast, duration of signs is 12 months. (d) IBC; erythema, edema, peau d’orange of the right breast, duration of signs 72 months.” von openi. License: (CC BY 2.5)

It is accountable for 1 – 4% of all mastocarcinomas, especially found in large mammae and, due to the lack of a defined palpable tumor, it is often hard to diagnose. Mammography and sonography often do not deliver distinct results.  As a possible differential diagnosis, in any case, a nonpuerpal mastitis, which appears suddenly and is accompanied with pain and fever, has to be ruled out.

Therapy includes neoadjuvant chemotherapy or radiation to be followed by surgery (modified radical mastectomy). Having a 5-year-survival-rate of only 5%, the prognosis of the inflammatory mastocarcinoma is poor.

Paget’s disease of the nipple

The Paget’s carcinoma grows intraepidermal ductal and appears in an eczematously changed nipple and/or areola. It may be accompanied a DCIS or an invasive ductal carcinoma.

Paget Disease of the Nipple

Image: “Scaly, erythematous, crusty and thickened plaque on the nipple of Paget Disease of the Breast” by Lily Chu. License: Public Domain

Since mammography is usually without pathological findings, exfoliative cytology is a proper way to detect the typical Paget-cells (large cells, bright cytoplasm and large round/oval nucleus). MRT-scans can be equally sensible.

For therapy, the modified radical mastectomy and, in individual cases, a breast-preserving therapy (BPT) comes into consideration, in which the therapy plan depends on the present type of carcinoma.

High magnification micrograph of extramammary Paget's disease

Image: “High magnification micrograph of extramammary Paget’s disease, abbreviated EMPD” by Nephron. License: (CC BY-SA 3.0)

Note: With an eczematous nipple, Paget’s disease should always be ruled out!

The further diagnostic and therapeutic steps can be found in the next article: The mastocarcinoma II – diagnosis, therapy and prognosis.

Popular Exam Questions Regarding Mammary Carcinoma

The correct answers can be found below the list of references.

Which of the named transformations is least typical of the typical clinical picture of breast cancer?

  1. Bloody fluid leaking out the nipple
  2. Swollen axillary lymph nodes
  3. Multiple lumps inside the breast
  4. Peau d’orange
  5. Eczematous transformation of the nipple

Which is the correct statement?

  1. Most frequently, breast cancer is located in the lower outer quadrant.
  2. Men cannot get breast cancer.
  3. Every 8th to 10th woman gets breast cancer during the course of her life.
  4. The patient’s age plays a minor role in the formation of breast cancer.
  5. Breast cancer is metastasizing lately.

A 52-year old patient presents with a redness and swelling of her left breast. According to the patient, this has developed slowly. During the examination, you notice hyperthermia of her left breast in comparison to her right one. Which diagnosis is the most likely?

  1. Paget’s disease of the nipple
  2. Nonpuerpal mastitis
  3. Comedo-like DCIS
  4. Inflammatory breast cancer
  5. Multifocal breast cancer


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